bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of relapsed or refractory classical Hodgkin lymphoma with the anti-PD-1, tislelizumab: results of a phase 2, single-arm, multicenter study
Authors: Song Yuqin , Gao Quanli , Zhang Huilai , Fan Lei , Zhou Jianfeng , Zou Dehui , Li Wei , Yang Haiyan , Liu Ting , Wang Quanshun , Lv Fangfang , Guo Haiyi , Yang Liudi , Elstrom Rebecca , Huang Jane , Novotny William , Wei Vivian , Zhu Jun 
Published: September 2019

AbstractPrognosis is poor for patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) after failure of or who are ineligible for autologous stem cell transplant. We evaluated the efficacy and safety of tislelizumab, an investigational anti-PD-1 monoclonal antibody, in phase 2, single-arm study in Chinese patients with R/R cHL. The primary endpoint was overall response rate as assessed by an independent review committee, according to the Lugano 2014 Classification. Seventy patients were enrolled in the study and received at least one dose of tislelizumab. After median follow-up of 9.8 months, 61 (87.1%) patients achieved an objective response, with 44 (62.9%) achieving a complete response (CR). The estimated 9-month progression-free survival rate was 74.5%. Most common grade ≥3 adverse events (AEs) were upper respiratory tract infection and pneumonitis. Infusion-related reactions occurred in 27 (38.6%) patients, and 27 patients (38.6%) experienced an immune-related AE, the most common of which was thyroid dysfunction. Eleven (15.7%) patients experienced at least one treatment-emergent AE leading to dose interruption or delay. No deaths occurred due to AEs. Treatment of patients with R/R cHL with tislelizumab was generally well tolerated and resulted in high overall response and CR rates, potentially translating into more durable responses for these patients.
Minocycline alters behavior, microglia and the gut microbiome in a trait-anxiety-dependent manner
Authors: Schmidtner Anna K. , Slattery David A. , Gläsner Joachim , Hiergeist Andreas , Gryksa Katharina , Malik Victoria A. , Hellmann-Regen Julian , Heuser Isabella , Baghai Thomas C. , Gessner André , Rupprecht Rainer , Di Benedetto Barbara , Neumann Inga D. 
Published: September 2019

AbstractMajor depressive disorder is the main cause of disability worldwide with imperfect treatment options. However, novel therapeutic approaches are currently discussed, from augmentation strategies to novel treatments targeting the immune system or the microbiome-gut-brain axis. Therefore, we examined the potential beneficial effects of minocycline, a tetracycline antibiotic with pleiotropic, immunomodulatory action, alone or as augmentation of escitalopram on behavior, prefrontal microglial density, and the gut microbiome in rats selectively bred for high anxiety-like behavior (HAB). We show that concomitant with their high innate anxiety and depression, HABs have lower microglial numbers in the infralimbic and prelimbic prefrontal cortex and an altered gut microbiota composition compared with controls. Three weeks of minocycline treatment alleviated the depressive-like phenotype, further reduced microglial density, exclusively in male HAB rats, and reduced plasma concentrations of pro-inflammatory cytokines. However, coadministration of escitalopram, which had no effect alone, prevented these minocycline-induced effects. Moreover, minocycline led to a robust shift in cecal microbial composition in both HABs and rats non-selected for anxiety-like behavior. Minocycline markedly increased relative abundance of Lachnospiraceae and Clostridiales Family XIII, families known for their butyrate production, with a corresponding increase and positive correlation in plasma 3-OH-butyrate levels in a trait-dependent manner. Thus, our data suggest that the antidepressant effect of minocycline is sex- and trait-dependent, associated with a reduced microglial number in the prefrontal cortex, and with changes in microbial composition and their metabolites. These results further support the microbiome-gut–brain axis as potential target in the treatment of depression.
On the warm bias in atmospheric reanalyses induced by the missing snow over Arctic sea-ice
Authors: Batrak Yurii , Müller Malte 
Published: September 2019

AbstractOver the past decades, the Arctic has been warming more than any other region in the world with profound socio-economic consequences. One of the key elements for understanding this rapid climate change is the surface energy budget. However, in the Arctic this budget is not consistently described across the various climate models, reanalyses and observation products. Recognising the physical causes of these inconsistencies is highly relevant for improving climate predictions and projections. Here we show that a 5 to 10 °C warm bias of the sea-ice surface temperature in global atmospheric reanalyses and weather forecasts is mainly caused by a missing representation of the snow layer on top of the sea-ice. Due to the low thermal conductivity of snow compared to sea-ice, a thin snow layer reduces the conductive heat flux much more efficiently than sea-ice, and thus insulates the cold atmosphere from the relatively warm ocean.
K63-linked ubiquitination regulates RIPK1 kinase activity to prevent cell death during embryogenesis and inflammation
Authors: Tang Yong , Tu Hailin , Zhang Jie , Zhao Xueqiang , Wang Yini , Qin Jun , Lin Xin 
Published: September 2019

AbstractReceptor-interacting protein kinase 1 (RIPK1) is a critical regulator of cell death through its kinase activity. However, how its kinase activity is regulated remains poorly understood. Here, we generate Ripk1K376R/K376R knock-in mice in which the Lys(K)63-linked ubiquitination of RIPK1 is impaired. The knock-in mice display an early embryonic lethality due to massive cell death that is resulted from reduced TAK1-mediated suppression on RIPK1 kinase activity and forming more TNFR1 complex II in Ripk1K376R/K376R cells in response to TNFα. Although TNFR1 deficiency delays the lethality, concomitant deletion of RIPK3 and Caspase8 fully prevents embryonic lethality of Ripk1K376R/K376R mice. Notably, Ripk1K376R/- mice are viable but develop severe systemic inflammation that is mainly driven by RIPK3-dependent signaling pathway, indicating that K63-linked ubiquitination on Lys376 residue of RIPK1 also contributes to inflammation process. Together, our study reveals the mechanism by which K63-linked ubiquitination on K376 regulates RIPK1 kinase activity to control cell death programs.
Generating keV ion distributions for nuclear reactions at near solid-density using intense short-pulse lasers
Authors: Kemp A. J. , Wilks S. C. , Hartouni E. P. , Grim G. 
Published: September 2019

AbstractOur understanding of a large range of astrophysical phenomena depends on a precise knowledge of charged particle nuclear reactions that occur at very low rates, which are difficult to measure under relevant plasma conditions. Here, we describe a method for generating dense plasmas at effective ion temperatures >20 keV, sufficient to induce measurable charged particle nuclear reactions. Our approach uses ultra-intense lasers to drive micron-sized, encapsulated nanofoam targets. Energetic electrons generated in the intense laser interaction pass through the foam, inducing a rapid expansion of the foam ions; this results in a hot, near-solid density plasma. We present the laser and target conditions necessary to achieve these conditions and illustrate the system performance using three-dimensional particle-in-cell simulations, outline potential applications and calculate expected nuclear reaction rates in the D(d,n) and 12C(p,γ) systems assuming CD, or CH aerogel foams.
Metal-coordinated sub-10 nm membranes for water purification
Authors: You Xinda , Wu Hong , Zhang Runnan , Su Yanlei , Cao Li , Yu Qianqian , Yuan Jinqiu , Xiao Ke , He Mingrui , Jiang Zhongyi 
Published: September 2019

AbstractUltrathin membranes with potentially high permeability are urgently demanded in water purification. However, their facile, controllable fabrication remains a grand challenge. Herein, we demonstrate a metal-coordinated approach towards defect-free and robust membranes with sub-10 nm thickness. Phytic acid, a natural strong electron donor, is assembled with metal ion-based electron acceptors to fabricate metal-organophosphate membranes (MOPMs) in aqueous solution. Metal ions with higher binding energy or ionization potential such as Fe3+ and Zr4+ can generate defect-free structure while MOPM-Fe3+ with superhydrophilicity is preferred. The membrane thickness is minimized to 8 nm by varying the ligand concentration and the pore structure of MOPM-Fe3+ is regulated by varying the Fe3+ content. The membrane with optimized MOPM-Fe3+ composition exhibits prominent water permeance (109.8 L m−2 h−1 bar−1) with dye rejections above 95% and superior stability. This strong-coordination assembly may enlighten the development of ultrathin high-performance membranes.
The mutational landscape of a prion-like domain
Authors: Bolognesi Benedetta , Faure Andre J. , Seuma Mireia , Schmiedel Jörn M. , Tartaglia Gian Gaetano , Lehner Ben 
Published: September 2019

AbstractInsoluble protein aggregates are the hallmarks of many neurodegenerative diseases. For example, aggregates of TDP-43 occur in nearly all cases of amyotrophic lateral sclerosis (ALS). However, whether aggregates cause cellular toxicity is still not clear, even in simpler cellular systems. We reasoned that deep mutagenesis might be a powerful approach to disentangle the relationship between aggregation and toxicity. We generated >50,000 mutations in the prion-like domain (PRD) of TDP-43 and quantified their toxicity in yeast cells. Surprisingly, mutations that increase hydrophobicity and aggregation strongly decrease toxicity. In contrast, toxic variants promote the formation of dynamic liquid-like condensates. Mutations have their strongest effects in a hotspot that genetic interactions reveal to be structured in vivo, illustrating how mutagenesis can probe the in vivo structures of unstructured proteins. Our results show that aggregation of TDP-43 is not harmful but protects cells, most likely by titrating the protein away from a toxic liquid-like phase.
EMS1 and BRI1 control separate biological processes via extracellular domain diversity and intracellular domain conservation
Authors: Zheng Bowen , Bai Qunwei , Wu Lei , Liu Huan , Liu Yuping , Xu Weijun , Li Guishuang , Ren Hongyan , She Xiaoping , Wu Guang 
Published: September 2019

AbstractIn flowering plants, EMS1 (Excess Microsporocytes 1) perceives TPD1 (Tapetum Determinant 1) to specify tapeta, the last somatic cell layer nurturing pollen development. However, the signaling components downstream of EMS1 are relatively unknown. Here, we use a molecular complementation approach to investigate the downstream components in EMS1 signaling. We show that the EMS1 intracellular domain is functionally interchangeable with that of the brassinosteroid receptor BRI1 (Brassinosteroid Insensitive 1). Furthermore, expressing EMS1 together with TPD1 in the BRI1 expression domain could partially rescue bri1 phenotypes, and led to the dephosphorylation of BES1, a hallmark of active BRI1 signaling. Conversely, expressing BRI1 in the EMS1 expression domain could partially rescue ems1 phenotypes. We further show that PpEMS1 and PpTPD1 from the early land plant Physcomitrella patens could completely rescue ems1 and tpd1 phenotypes, respectively. We propose that EMS1 and BRI1 have evolved distinct extracellular domains to control different biological processes but can act via a common intracellular signaling pathway.
A chemo-enzymatic oxidation cascade to activate C–H bonds with in situ generated H2O2
Authors: Freakley Simon J. , Kochius Svenja , van Marwijk Jacqueline , Fenner Caryn , Lewis Richard J. , Baldenius Kai , Marais Sarel S. , Opperman Diederik J. , Harrison Susan T. L. , Alcalde Miguel , Smit Martha S. , Hutchings Graham J. 
Published: September 2019

AbstractContinuous low-level supply or in situ generation of hydrogen peroxide (H2O2) is essential for the stability of unspecific peroxygenases, which are deemed ideal biocatalysts for the selective activation of C–H bonds. To envisage potential large scale applications of combined catalytic systems the reactions need to be simple, efficient and produce minimal by-products. We show that gold-palladium nanoparticles supported on TiO2 or carbon have sufficient activity at ambient temperature and pressure to generate H2O2 from H2 and O2 and supply the oxidant to the engineered unspecific heme-thiolate peroxygenase PaDa-I. This tandem catalyst combination facilitates efficient oxidation of a range of C-H bonds to hydroxylated products in one reaction vessel with only water as a by-product under conditions that could be easily scaled.
Resequencing 545 ginkgo genomes across the world reveals the evolutionary history of the living fossil
Authors: Zhao Yun-Peng , Fan Guangyi , Yin Ping-Ping , Sun Shuai , Li Ning , Hong Xiaoning , Hu Gang , Zhang He , Zhang Fu-Min , Han Jing-Dan , Hao Ya-Jun , Xu Qiwu , Yang Xianwei , Xia Wenjie , Chen Wenbin , Lin Han-Yang , Zhang Rui , Chen Jiang , Zheng Xiao-Ming , Lee Simon Ming-Yuen , Lee Joongku , Uehara Koichi , Wang Jian , Yang Huanming , Fu Cheng-Xin , Liu Xin , Xu Xun , Ge Song 
Published: September 2019

AbstractAs Charles Darwin anticipated, living fossils provide excellent opportunities to study evolutionary questions related to extinction, competition, and adaptation. Ginkgo (Ginkgo bilobaL.) is one of the oldest living plants and a fascinating example of how people have saved a species from extinction and assisted its resurgence. By resequencing 545 genomes of ginkgo trees sampled from 51 populations across the world, we identify three refugia in China and detect multiple cycles of population expansion and reduction along with glacial admixture between relict populations in the southwestern and southern refugia. We demonstrate multiple anthropogenic introductions of ginkgo from eastern China into different continents. Further analyses reveal bioclimatic variables that have affected the geographic distribution of ginkgo and the role of natural selection in ginkgo’s adaptation and resilience. These investigations provide insights into the evolutionary history of ginkgo trees and valuable genomic resources for further addressing various questions involving living fossil species.
Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making
Authors: Zanotelli Matthew R. , Rahman-Zaman Aniqua , VanderBurgh Jacob A. , Taufalele Paul V. , Jain Aadhar , Erickson David , Bordeleau Francois , Reinhart-King Cynthia A. 
Published: September 2019

AbstractCell migration during the invasion-metastasis cascade requires cancer cells to navigate a spatially complex microenvironment that presents directional choices to migrating cells. Here, we investigate cellular energetics during migration decision-making in confined spaces. Theoretical and experimental data show that energetic costs for migration through confined spaces are mediated by a balance between cell and matrix compliance as well as the degree of spatial confinement to direct decision-making. Energetic costs, driven by the cellular work needed to generate force for matrix displacement, increase with increasing cell stiffness, matrix stiffness, and degree of spatial confinement, limiting migration. By assessing energetic costs between possible migration paths, we can predict the probability of migration choice. Our findings indicate that motility in confined spaces imposes high energetic demands on migrating cells, and cells migrate in the direction of least confinement to minimize energetic costs. Therefore, therapeutically targeting metabolism may limit cancer cell migration and metastasis.
Depletion of HuR in murine skeletal muscle enhances exercise endurance and prevents cancer-induced muscle atrophy
Authors: Janice Sánchez Brenda , Tremblay Anne-Marie K. , Leduc-Gaudet Jean-Philippe , Hall Derek T. , Kovacs Erzsebet , Ma Jennifer F. , Mubaid Souad , Hallauer Patricia L. , Phillips Brittany L. , Vest Katherine E. , Corbett Anita H. , Kontoyiannis Dimitris L. , Hussain Sabah N. A. , Hastings Kenneth E. M. , Di Marco Sergio , Gallouzi Imed-Eddine 
Published: September 2019

AbstractThe master posttranscriptional regulator HuR promotes muscle fiber formation in cultured muscle cells. However, its impact on muscle physiology and function in vivo is still unclear. Here, we show that muscle-specific HuR knockout (muHuR-KO) mice have high exercise endurance that is associated with enhanced oxygen consumption and carbon dioxide production. muHuR-KO mice exhibit a significant increase in the proportion of oxidative type I fibers in several skeletal muscles. HuR mediates these effects by collaborating with the mRNA decay factor KSRP to destabilize the PGC-1α mRNA. The type I fiber-enriched phenotype of muHuR-KO mice protects against cancer cachexia-induced muscle loss. Therefore, our study uncovers that under normal conditions HuR modulates muscle fiber type specification by promoting the formation of glycolytic type II fibers. We also provide a proof-of-principle that HuR expression can be targeted therapeutically in skeletal muscles to combat cancer-induced muscle wasting.
Floquet Chern insulators of light
Authors: He Li , Addison Zachariah , Jin Jicheng , Mele Eugene J. , Johnson Steven G. , Zhen Bo 
Published: September 2019

AbstractAchieving topologically-protected robust transport in optical systems has recently been of great interest. Most studied topological photonic structures can be understood by solving the eigenvalue problem of Maxwell’s equations for static linear systems. Here, we extend topological phases into dynamically driven systems and achieve a Floquet Chern insulator of light in nonlinear photonic crystals (PhCs). Specifically, we start by presenting the Floquet eigenvalue problem in driven two-dimensional PhCs. We then define topological invariant associated with Floquet bands, and show that topological band gaps with non-zero Chern number can be opened by breaking time-reversal symmetry through the driving field. Finally, we numerically demonstrate the existence of chiral edge states at the interfaces between a Floquet Chern insulator and normal insulators, where the transport is non-reciprocal and uni-directional. Our work paves the way to further exploring topological phases in driven optical systems and their optoelectronic applications.
Step-wise endoscopic approach to palliative bilateral biliary drainage for unresectable advanced malignant hilar obstruction
Authors: Choi Jin Ho , Lee Sang Hyub , You Min Su , Shin Bang-sup , Choi Young Hoon , Kang Jinwoo , Jang Sunguk , Paik Woo Hyun , Ryu Ji Kon , Kim Yong-Tae 
Published: September 2019

AbstractThe ideal type of stent utilized at index endoscopic retrograde cholangiopancreatography (ERCP) in management of malignant hilar obstruction (MHO) remains unclear. We aimed to determine the ideal stent choice in patients with MHO. In this retrospective study, patients with unresectable MHO were separated into the plastic stent (PS) group and the self-expandable metal stent (SEMS) group. The primary outcome was the risk and rate of rescue percutaneous transhepatic biliary drainage (PTBD). The secondary outcomes were the progression-free survival, the overall survival and the PTBD-free period (days). Thirty-six patients in the PS group and 38 patients in the SEMS group were enrolled. The risk for PTBD was higher in SEMS group (HR = 2.205, 95% C.I. 0.977–4.977, P = 0.057). The rate of PTBD was significantly lower in the PS group. (22.2% vs 50.0%, P = 0.017) There were no differences in overall survival and progression-free survival (410 and 269 in the PS group, 395 and 266 in the SEMS group, P = 0.663 and P = 0.757). The PTBD-free period was significantly longer in the PS group. (836.43 vs 586.40, P = 0.039) Although comparable in clinical efficacy, utilization of PS at index ERCP may reduce patient’s discomfort by avoiding PTBD and prolonging PTBD-free period in patients with MHO.
Suitability of ultrasound-guided fine-needle aspiration biopsy for transcriptome sequencing of the canine prostate
Authors: Thiemeyer H. , Taher L. , Schille J. T. , Harder L. , Hungerbuehler S. O. , Mischke R. , Hewicker-Trautwein M. , Kiełbowicz Z. , Brenig B. , Schütz E. , Beck J. , Murua Escobar H. , Nolte I. 
Published: September 2019

AbstractUltrasound-guided fine-needle aspiration (US-FNA) biopsy is a widely used minimally invasive sampling procedure for cytological diagnosis. This study investigates the feasibility of using US-FNA samples for both cytological diagnosis and whole transcriptome RNA-sequencing analysis (RNA-Seq), with the ultimate aim of improving canine prostate cancer management. The feasibility of the US-FNA procedure was evaluatedintra vitamon 43 dogs. Additionally, aspirates from 31 euthanised dogs were collected for standardising the procedure. Each aspirate was separated into two subsamples: for cytology and RNA extraction. Additional prostate tissue samples served as control for RNA quantity and quality evaluation, and differential expression analysis. The US-FNA sampling procedure was feasible in 95% of dogs. RNA isolation of US-FNA samples was successfully performed using phenol-chloroform extraction. The extracted RNA of 56% of a subset of US-FNA samples met the quality requirements for RNA-Seq. Expression analysis revealed that only 153 genes were exclusively differentially expressed between non-malignant US-FNAs and tissues. Moreover, only 36 differentially expressed genes were associated with the US-FNA sampling technique and unrelated to the diagnosis. Furthermore, the gene expression profiles clearly distinguished between non-malignant and malignant samples. This proves US-FNA to be useful for molecular profiling.
Dynamics of atmospheric 131I in radioactive plumes in eastern Japan immediately after the Fukushima accident by analysing published data
Authors: Tsuruta Haruo , Moriguchi Yuichi , Nakajima Teruyuki 
Published: September 2019

AbstractThe spatio-temporal distribution of atmospheric radioiodine immediately after the Fukushima Daiichi Nuclear Power Plant (FD1NPP) accident has not yet been clarified due to very limited observed data, compared with atmospheric radiocaesium data. Here, we first revealed that the ratios of 131I (decay-corrected to March 11, 2011) to 137Cs in radioactive plumes were divided into three groups (A, B, and C) by analysing all published data on atmospheric 131I concentrations independently measured immediately after the accident in eastern Japan. Groups A and C were found regardless of whether the measurement sites were located in eastern Fukushima or Kantou areas, while group B was observed only in the eastern Kantou area. The ratios in group A were approximately equal to 10 for the plumes on March 15, March 20, and on the morning of March 21, and those in group B were approximately 75 on March 16. Their possible sources were Unit 2 and/or Unit 3. In contrast, the ratios in group C were approximately equal to 360, much higher than those of groups A and B, and were observed from the afternoon of March 21 to March 25. These high 131I concentrations could be released after water supply to FD1NPP.