bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of a novel high pressure non-compliant balloon for tibial atherosclerotic lesions in Asian patients with chronic limb threatening ischaemia
Authors: Tang Tjun Yip , Lee Shaun Qing Wei , Chan Sze Ling , Yap Charyl Jia Qi , Soon Shereen Xue Yun , Chong Tze Tec , Choke Edward Tieng Chek , Yan Bryan P.Y. 
Published: July 2020

Summary: Background: The aim was to evaluate the safety and efficacy of a high pressure, non-compliant balloon in the treatment of infrapopliteal occlusive disease in Asian patients with chronic limb threatening ischaemia (CLTI) from Singapore. Patients and methods: Prospective, multi-centre, single arm, non-randomized study. Immediate technical success, 6-month primary vessel patency (determined by Duplex ultrasonography), limb salvage, one-year clinically driven target lesion re-intervention (TLR) and amputation free survival (AFS) were the efficacy endpoints of interest. Results: 86 patients (63% males, mean age 68.9 ± 9.9 years) were enrolled over a 15-month period. Diabetes mellitus (DM) and end-stage renal failure (ESRF) were present in 94% and 38% of patients respectively. All had some degree of tissue loss at baseline (Rutherford scale 5 and 6 = 91% and 9% respectively). Of the 86 legs, 72% had 3 crural vessel disease and 84% had moderate/severe vessel wall calcification. 90% had > = 1 TASC D tibial lesion. Acute technical success was 89%. One month mortality was 3.5% and one-year freedom from TLR was 91%. 6-month tibial patency was 73%. 54/66 (82%) patients had at least one target treated tibial artery open at 6 months. A lower baseline toe pressure (OR 1.03, 95%CI 1.00–1.05) and elastic recoil post angioplasty (OR 0.20, 95%CI 0.05–0.79) were associated with a worse 6 month tibial patency. One-year AFS was 67%. 47/66 (71%) patients had a clinical improvement of at least one Rutherford class at 6 months and 52/59 (88%) experienced complete wound healing at 12 months. Conclusions: Use of a high pressure non-compliant balloon is safe and efficacious in treating highly complex infra-popliteal atherosclerotic lesions in an otherwise challenging population of CLTI patients with a high incidence of DM and ESRF. It is associated with highly satisfactory acute technical success, 6-month target lesion patency and one-year limb salvage.
Outer Radiation Belt Electron Lifetime Model Based on Combined Van Allen Probes and Cluster VLF Measurements
Authors: Aryan Homayon , Agapitov Oleksiy V. , Artemyev Anton , Mourenas Didier , Balikhin Michael A. , Boynton Richard , Bortnik Jacob 
Published: July 2020

AbstractThe flux of energetic electrons in the outer radiation belt shows a high variability. The interactions of electrons with very low frequency (VLF) chorus waves play a significant role in controlling the flux variation of these particles. Quantifying the effects of these interactions is crucially important for accurately modeling the global dynamics of the outer radiation belt and to provide a comprehensive description of electron flux variations over a wide energy range (from the source population of 30 keV electrons up to the relativistic core population of the outer radiation belt). Here, we use a synthetic chorus wave model based on a combined database compiled from the Van Allen Probes and Cluster spacecraft VLF measurements to develop a comprehensive parametric model of electron lifetimes as a function of L‐shell, electron energy, and geomagnetic activity. The wave model takes into account the wave amplitude dependence on geomagnetic latitude, wave normal angle distribution, and variations of wave frequency with latitude. We provide general analytical formulas to estimate electron lifetimes as a function of L‐shell (for L = 3.0 to L = 6.5), electron energy (from 30 keV to 2 MeV), and geomagnetic activity parameterized by the AE index. The present model lifetimes are compared to previous studies and analytical results and also show a good agreement with measured lifetimes of 30 to 300 keV electrons at geosynchronous orbit.
ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk
Authors: Sekiguchi Mariko , Sobue Akira , Kushima Itaru , Wang Chenyao , Arioka Yuko , Kato Hidekazu , Kodama Akiko , Kubo Hisako , Ito Norimichi , Sawahata Masahito , Hada Kazuhiro , Ikeda Ryosuke , Shinno Mio , Mizukoshi Chikara , Tsujimura Keita , Yoshimi Akira , Ishizuka Kanako , Takasaki Yuto , Kimura Hiroki , Xing Jingrui , Yu Yanjie , Yamamoto Maeri , Okada Takashi , Shishido Emiko , Inada Toshiya , Nakatochi Masahiro , Takano Tetsuya , Kuroda Keisuke , Amano Mutsuki , Aleksic Branko , Yamomoto Takashi , Sakuma Tetsushi , Aida Tomomi , Tanaka Kohichi , Hashimoto Ryota , Arai Makoto , Ikeda Masashi , Iwata Nakao , Shimamura Teppei , Nagai Taku , Nabeshima Toshitaka , Kaibuchi Kozo , Yamada Kiyofumi , Mori Daisuke , Ozaki Norio 
Published: July 2020

AbstractSchizophrenia (SCZ) is known to be a heritable disorder; however, its multifactorial nature has significantly hampered attempts to establish its pathogenesis. Therefore, in this study, we performed genome-wide copy-number variation (CNV) analysis of 2940 patients with SCZ and 2402 control subjects and identified a statistically significant association between SCZ and exonic CNVs in the ARHGAP10 gene. ARHGAP10 encodes a member of the RhoGAP superfamily of proteins that is involved in small GTPase signaling. This signaling pathway is one of the SCZ-associated pathways and may contribute to neural development and function. However, the ARHGAP10 gene is often confused with ARHGAP21, thus, the significance of ARHGAP10 in the molecular pathology of SCZ, including the expression profile of the ARHGAP10 protein, remains poorly understood. To address this issue, we focused on one patient identified to have both an exonic deletion and a missense variant (p.S490P) in ARHGAP10. The missense variant was found to be located in the RhoGAP domain and was determined to be relevant to the association between ARHGAP10 and the active form of RhoA. We evaluated ARHGAP10 protein expression in the brains of reporter mice and generated a mouse model to mimic the patient case. The model exhibited abnormal emotional behaviors, along with reduced spine density in the medial prefrontal cortex (mPFC). In addition, primary cultured neurons prepared from the mouse model brain exhibited immature neurites in vitro. Furthermore, we established induced pluripotent stem cells (iPSCs) from this patient, and differentiated them into tyrosine hydroxylase (TH)-positive neurons in order to analyze their morphological phenotypes. TH-positive neurons differentiated from the patient-derived iPSCs exhibited severe defects in both neurite length and branch number; these defects were restored by the addition of the Rho-kinase inhibitor, Y-27632. Collectively, our findings suggest that rare ARHGAP10 variants may be genetically and biologically associated with SCZ and indicate that Rho signaling represents a promising drug discovery target for SCZ treatment.
Genome-wide association study of cognitive function in diverse Hispanics/Latinos: results from the Hispanic Community Health Study/Study of Latinos
Authors: Jian Xueqiu , Sofer Tamar , Tarraf Wassim , Bressler Jan , Faul Jessica D. , Zhao Wei , Ratliff Scott M. , Lamar Melissa , Launer Lenore J. , Laurie Cathy C. , Schneiderman Neil , Weir David R. , Wright Clinton B. , Yaffe Kristine , Zeng Donglin , DeCarli Charles , Mosley Thomas H. , Smith Jennifer A. , González Hector M. , Fornage Myriam 
Published: July 2020

AbstractCognitive function such as reasoning, attention, memory, and language is strongly correlated with brain aging. Compared to non-Hispanic whites, Hispanics/Latinos have a higher risk of cognitive impairment and dementia. The genetic determinants of cognitive function have not been widely explored in this diverse and admixed population. We conducted a genome-wide association analysis of cognitive function in up to 7600 middle aged and older Hispanics/Latinos (mean = 55 years) from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). Four cognitive measures were examined: the Brief Spanish English Verbal Learning Test (B-SEVLT), the Word Fluency Test (WFT), the Digit Symbol Substitution Test (DSST), the Six-Item Screener (SIS). Four novel loci were identified: one for B-SEVLT at 4p14, two for WFT at 3p14.1 and 6p21.32, and one for DSST at 10p13. These loci implicate genes highly expressed in brain and previously connected to neurological diseases (UBE2K,FRMD4B, theHLAgene complex). By applying tissue-specific gene expression prediction models to our genotype data, additional genes highly expressed in brain showed suggestive associations with cognitive measures possibly indicating novel biological mechanisms, includingIFT122in the hippocampus for SIS,SNX31in the basal ganglia for B-SEVLT,RPS6KB2in the frontal cortex for WFT, andCSPG5in the hypothalamus for DSST. These findings provide new information about the genetic determinants of cognitive function in this unique population. In addition, we derived a measure of general cognitive function based on these cognitive tests and generated genome-wide association summary results, providing a resource to the research community for comparison, replication, and meta-analysis in future genetic studies in Hispanics/Latinos.
Applying dimensional psychopathology: transdiagnostic associations among regional homogeneity, leptin and depressive symptoms
Authors: Wei Yan-ge , Duan Jia , Womer Fay Y. , Zhu Yue , Yin Zhiyang , Cui Lingling , Li Chao , Liu Zhuang , Wei Shengnan , Jiang Xiaowei , Zhang Yanbo , Zhang Xizhe , Tang Yanqing , Wang Fei 
Published: July 2020

AbstractDimensional psychopathology and its neurobiological underpinnings could provide important insights into major psychiatric disorders, including major depressive disorder, bipolar disorder and schizophrenia. In a dimensional transdiagnostic approach, we examined depressive symptoms and their relationships with regional homogeneity and leptin across major psychiatric disorders. A total of 728 participants (including 403 patients with major psychiatric disorders and 325 age–gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging at a single site. We obtained plasma leptin levels and depressive symptom measures (Hamilton Depression Rating Scale (HAMD)) within 24 h of scanning and compared the regional homogeneity (ReHo), plasma leptin levels and HAMD total score and factor scores between patients and healthy controls. To reveal the potential relationships, we performed correlational and mediational analyses. Patients with major psychiatric disorders had significant lower ReHo in primary sensory and visual association cortices and higher ReHo in the frontal cortex and angular gyrus; plasma leptin levels were also elevated. Furthermore, ReHo alterations, leptin and HAMD factor scores had significant correlations. We also found that leptin mediated the transdiagnostic relationships among ReHo alterations in primary somatosensory and visual association cortices, core depressive symptoms and body mass index. The transdiagnostic associations we demonstrated support the common neuroanatomical substrates and neurobiological mechanisms. Moreover, leptin could be an important association among ReHo, core depressive symptoms and body mass index, suggesting a potential therapeutic target for dimensional depressive symptoms across major psychiatric disorders.
Cancer immunotherapy with γδ T cells: many paths ahead of us
Authors: Kabelitz Dieter , Serrano Ruben , Kouakanou Léonce , Peters Christian , Kalyan Shirin 
Published: July 2020

Abstractγδ T cells play uniquely important roles in stress surveillance and immunity for infections and carcinogenesis. Human γδ T cells recognize and kill transformed cells independently of human leukocyte antigen (HLA) restriction, which is an essential feature of conventional αβ T cells. Vγ9Vδ2 γδ T cells, which prevail in the peripheral blood of healthy adults, are activated by microbial or endogenous tumor-derived pyrophosphates by a mechanism dependent on butyrophilin molecules. γδ T cells expressing other T cell receptor variable genes, notably Vδ1, are more abundant in mucosal tissue. In addition to the T cell receptor, γδ T cells usually express activating natural killer (NK) receptors, such as NKp30, NKp44, or NKG2D which binds to stress-inducible surface molecules that are absent on healthy cells but are frequently expressed on malignant cells. Therefore, γδ T cells are endowed with at least two independent recognition systems to sense tumor cells and to initiate anticancer effector mechanisms, including cytokine production and cytotoxicity. In view of their HLA-independent potent antitumor activity, there has been increasing interest in translating the unique potential of γδ T cells into innovative cellular cancer immunotherapies. Here, we discuss recent developments to enhance the efficacy of γδ T cell-based immunotherapy. This includes strategies for in vivo activation and tumor-targeting of γδ T cells, the optimization of in vitro expansion protocols, and the development of gene-modified γδ T cells. It is equally important to consider potential synergisms with other therapeutic strategies, notably checkpoint inhibitors, chemotherapy, or the (local) activation of innate immunity.
Oceanographic features and limited dispersal shape the population genetic structure of the vase sponge Ircinia campana in the Greater Caribbean
Authors: Griffiths Sarah M. , Butler Mark J. , Behringer Donald C. , Pérez Thierry , Preziosi Richard F. 
Published: July 2020

AbstractUnderstanding population genetic structure can help us to infer dispersal patterns, predict population resilience and design effective management strategies. For sessile species with limited dispersal, this is especially pertinent because genetic diversity and connectivity are key aspects of their resilience to environmental stressors. Here, we describe the population structure ofIrcinia campana, a common Caribbean sponge subject to mass mortalities and disease. Microsatellites were used to genotype 440 individuals from 19 sites throughout the Greater Caribbean. We found strong genetic structure across the region, and significant isolation by distance across the Lesser Antilles, highlighting the influence of limited larval dispersal. We also observed spatial genetic structure patterns congruent with oceanography. This includes evidence of connectivity between sponges in the Florida Keys and the southeast coast of the United States (>700 km away) where the oceanographic environment is dominated by the strong Florida Current. Conversely, the population in southern Belize was strongly differentiated from all other sites, consistent with the presence of dispersal-limiting oceanographic features, including the Gulf of Honduras gyre. At smaller spatial scales (<100 km), sites showed heterogeneous patterns of low-level but significant genetic differentiation (chaotic genetic patchiness), indicative of temporal variability in recruitment or local selective pressures. Genetic diversity was similar across sites, but there was evidence of a genetic bottleneck at one site in Florida where past mass mortalities have occurred. These findings underscore the relationship between regional oceanography and weak larval dispersal in explaining population genetic patterns, and could inform conservation management of the species.
B cell zone reticular cell microenvironments shape CXCL13 gradient formation
Authors: Cosgrove Jason , Novkovic Mario , Albrecht Stefan , Pikor Natalia B. , Zhou Zhaoukun , Onder Lucas , Mörbe Urs , Cupovic Jovana , Miller Helen , Alden Kieran , Thuery Anne , O’Toole Peter , Pinter Rita , Jarrett Simon , Taylor Emily , Venetz Daniel , Heller Manfred , Uguccioni Mariagrazia , Legler Daniel F. , Lacey Charles J. , Coatesworth Andrew , Polak Wojciech G. , Cupedo Tom , Manoury Bénedicte , Thelen Marcus , Stein Jens V. , Wolf Marlene , Leake Mark C. , Timmis Jon , Ludewig Burkhard , Coles Mark C. 
Published: July 2020

AbstractThrough the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients.
Murine models of IDH-wild-type glioblastoma exhibit spatial segregation of tumor initiation and manifestation during evolution
Authors: Li Yinghua , Li Bo , Li Wei , Wang Yuan , Akgül Seçkin , Treisman Daniel M. , Heist Kevin A. , Pierce Brianna R. , Hoff Benjamin , Ho Cheng-Ying , Ferguson David O. , Rehemtulla Alnawaz , Zheng Siyuan , Ross Brian D. , Li Jun Z. , Zhu Yuan 
Published: July 2020

AbstractRecent characterization of spatiotemporal genomic architecture of IDH-wild-type multifocal glioblastomas (M-GBMs) suggests a clinically unobserved common-ancestor (CA) with a less aggressive phenotype, generating highly genetically divergent malignant gliomas/GBMs in distant brain regions. Using serial MRI/3D-reconstruction, whole-genome sequencing and spectral karyotyping-based single-cell phylogenetic tree building, we show two distinct types of tumor evolution in p53-mutant driven mouse models. Malignant gliomas/GBMs grow as a single mass (Type 1) and multifocal masses (Type 2), respectively, despite both exhibiting loss of Pten/chromosome 19 (chr19) and PI3K/Akt activation with sub-tetraploid/4N genomes. Analysis of early biopsied and multi-segment tumor tissues reveals no evidence of less proliferative diploid/2N lesions in Type 1 tumors. Strikingly, CA-derived relatively quiescent tumor precursors with ancestral diploid/2N genomes and normal Pten/chr19 are observed in the subventricular zone (SVZ), but are distantly segregated from multi focal Type 2 tumors. Importantly, PI3K/Akt inhibition by Rictor/mTORC2 deletion blocks distant dispersal, restricting glioma growth in the SVZ.
The Movember Prostate Cancer Landscape Analysis: an assessment of unmet research needs
Authors: Kouspou Michelle M. , Fong Jenna E. , Brew Nadine , Hsiao Sarah T. F. , Davidson Seanna L. , Choyke Peter L. , Crispino Tony , Jain Suneil , Jenster Guido W. , Knudsen Beatrice S. , Millar Jeremy L. , Mittmann Nicole , Ryan Charles J. , Tombal Bertrand , Buzza Mark 
Published: July 2020

AbstractProstate cancer is a heterogeneous cancer with widely varying levels of morbidity and mortality. Approaches to prostate cancer screening, diagnosis, surveillance, treatment and management differ around the world. To identify the highest priority research needs across the prostate cancer biomedical research domain, Movember conducted a landscape analysis with the aim of maximizing the effect of future research investment through global collaborative efforts and partnerships. A global Landscape Analysis Committee (LAC) was established to act as an independent group of experts across urology, medical oncology, radiation oncology, radiology, pathology, translational research, health economics and patient advocacy. Men with prostate cancer and thought leaders from a variety of disciplines provided a range of key insights through a range of interviews. Insights were prioritized against predetermined criteria to understand the areas of greatest unmet need. From these efforts, 17 research needs in prostate cancer were agreed on and prioritized, and 3 received the maximum prioritization score by the LAC: first, to establish more sensitive and specific tests to improve disease screening and diagnosis; second, to develop indicators to better stratify low-risk prostate cancer for determining which men should go on active surveillance; and third, to integrate companion diagnostics into randomized clinical trials to enable prediction of treatment response. On the basis of the findings from the landscape analysis, Movember will now have an increased focus on addressing the specific research needs that have been identified, with particular investment in research efforts that reduce disease progression and lead to improved therapies for advanced prostate cancer.
The effects of anthropogenic and volcanic aerosols and greenhouse gases on twentieth century Sahel precipitation
Authors: Herman Rebecca Jean , Giannini Alessandra , Biasutti Michela , Kushnir Yochanan 
Published: July 2020

AbstractThere is little scientific consensus on the importance of external climate forcings—including anthropogenic aerosols, volcanic aerosols, and greenhouse gases (GHG)—relative to each other and to internal variability in dictating past and future Sahel rainfall. We address this query by relating a 3-tiered multi-model mean (MMM) over the Climate Model Intercomparison Project phase 5 “twentieth century” and pre-Industrial control simulations to observations. The comparison of single-forcing and historical simulations highlights the importance of anthropogenic and volcanic aerosols over GHG in generating forced Sahel rainfall variability in models. However, the forced MMM only accounts for a small fraction of observed variance. A residual consistency test shows that simulated internal variability cannot explain the residual observed multidecadal variability, and points to model deficiency in simulating multidecadal variability in the forced response, internal variability, or both.
Variations in foliar carbon:nitrogen and nitrogen:phosphorus ratios under global change: a meta-analysis of experimental field studies
Authors: Xu Shan , Sardans Jordi , Zhang Jinlong , Peñuelas Josep 
Published: July 2020

AbstractFoliar-level stoichiometry plays an important role in ecosystem elemental cycling. Shifts in foliar ratios of carbon to nitrogen (C:N) and nitrogen to phosphorus (N:P) in response to global change can therefore have a large impact upon ecosystem function. We conducted a meta-analysis with 2,236 paired observations from 123 published studies to investigate the responses of foliar C:N and N:P ratios to experimental global change treatments, i.e. warming, increased precipitation, drought, N addition and elevated carbon dioxide concentration (eCO2), in field conditions. Foliar C:N and N:P ratios were neither affected by warming nor by increased precipitation. Foliar C:N ratio increased with drought and eCO2, and decreased with N addition. Foliar N:P ratios declined with eCO2, and increased under drought and N addition. Our results suggested the responses of the C:N ratio to global change were mainly related to shifts in foliar [N], whereas changes in the N:P ratio were related to the responses of both [N] and [P]. Moreover, the response magnitude of foliar N:P ratio decreased with treatment duration under increased precipitation, N addition and eCO2. Our findings are important for our understanding of plant nutrient dynamic and modeling of nutrient biogeochemistry under global change.