bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term follow-up of cladribine treatment in hairy cell leukemia: 30-year experience in a multicentric Italian study
Authors: Pagano Livio , Criscuolo Marianna , Broccoli Alessandro , Piciocchi Alfonso , Varettoni Marzia , Galli Eugenio , Anastasia Antonella , Cantonetti Maria , Trentin Livio , Kovalchuk Sofia , Orsucci Lorella , Frustaci Annamaria , Spolzino Angelica , Volpetti Stefano , Annibali Ombretta , Storti Sergio , Stelitano Caterina , Marchesi Francesco , Offidani Massimo , Casadei Beatrice , Nizzoli Maria Elena , De Luca Maria Lucia , Fianchi Luana , Motta Marina , Guarnera Luca , Simonetti Edoardo , Visentin Andrea , Vassallo Francesco , Deodato Marina , Sarlo Chiara , Olivieri Attilio , Falini Brunangelo , Pulsoni Alessandro , Tiacci Enrico , Zinzani Pier Luigi 
Published: July 2022

AbstractHairy cell leukemia (HCL) is a rare lymphoproliferative disease with an excellent prognosis after treatment with cladribine (2CDA), although relapse may occur during follow-up. The aim of the study is to review the efficacy, safety, long-term remission rate, and overall survival (OS) in those patients who received 2CDA as first-line treatment. We retrospectively reviewed data of HCL patients treated with 2CDA between March 1991 and May 2019 at 18 Italian Hematological centers: 513 patients were evaluable for study purpose. The median age was 54 years (range 24–88) and ECOG was 0 in 84.9% of cases. A total of 330 (64.3%) patients received 2CDA intravenously and 183 (35.7%) subcutaneously. ORR was 91.8%: CR was obtained in 335 patients (65.3%), PR in 96 (18.7%), and hematological response in 40 (7.8%) patients; in 42 (8.2%) no response was observed. Hemoglobin value (p = 0.044), frequency of circulating hairy cells (p = 0.039), recovery of absolute neutrophil count (p = 0.006), and normalization of spleen (p ≤ 0.001) were associated with CR compared to PR in univariable analysis. At a median follow-up of 6.83 years (range 0.04–28.52), the median time to relapse was 12.2 years. A significant difference in duration of response was identified between patients that obtained a CR and PR (19.4 years versus 4.8 years, p < 0.0001). Non-hematological grade 3 or higher early toxicity was reported in 103 (20.1%) patients. Median OS was not reached: 95.3%, 92.4%, and 81.8% of patients were estimated to be alive at 5, 10, and 15 years, respectively. Forty-nine patients died (9.5%), following an infection in 14 cases (2.7%), natural causes in 14 (2.7%), cardiovascular events in 13 (2.5%), a second neoplasm in 6 (1.2%), and progression of HCL in 2 cases (0.4%). Following treatment of HCL with 2CDA, 80% of patients are estimated to be alive 15 years after diagnosis.
BRD9 degraders as chemosensitizers in acute leukemia and multiple myeloma
Authors: Weisberg Ellen , Chowdhury Basudev , Meng Chengcheng , Case Abigail E. , Ni Wei , Garg Swati , Sattler Martin , Azab Abdel Kareem , Sun Jennifer , Muz Barbara , Sanchez Dana , Toure Anthia , Stone Richard M. , Galinsky Ilene , Winer Eric , Gleim Scott , Gkountela Sofia , Kedves Alexia , Harrington Edmund , Abrams Tinya , Zoller Thomas , Vaupel Andrea , Manley Paul , Faller Michael , Chung BoYee , Chen Xin , Busenhart Philipp , Stephan Christine , Calkins Keith , Bonenfant Debora , Thoma Claudio R. , Forrester William , Griffin James D. 
Published: July 2022

AbstractBromodomain-containing protein 9 (BRD9), an essential component of the SWI/SNF chromatin remodeling complex termed ncBAF, has been established as a therapeutic target in a subset of sarcomas and leukemias. Here, we used novel small molecule inhibitors and degraders along with RNA interference to assess the dependency on BRD9 in the context of diverse hematological malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and multiple myeloma (MM) model systems. Following depletion of BRD9 protein, AML cells undergo terminal differentiation, whereas apoptosis was more prominent in ALL and MM. RNA-seq analysis of acute leukemia and MM cells revealed both unique and common signaling pathways affected by BRD9 degradation, with common pathways including those associated with regulation of inflammation, cell adhesion, DNA repair and cell cycle progression. Degradation of BRD9 potentiated the effects of several chemotherapeutic agents and targeted therapies against AML, ALL, and MM. Our findings support further development of therapeutic targeting of BRD9, alone or combined with other agents, as a novel strategy for acute leukemias and MM.
GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells
Authors: Palmisano Biagio , Labella Rossella , Donsante Samantha , Remoli Cristina , Spica Emanuela , Coletta Ilenia , Farinacci Giorgia , Dello Spedale Venti Michele , Saggio Isabella , Serafini Marta , Robey Pamela Gehron , Corsi Alessandro , Riminucci Mara 
Published: July 2022

AbstractThe Gsα/cAMP signaling pathway mediates the effect of a variety of hormones and factors that regulate the homeostasis of the post-natal skeleton. Hence, the dysregulated activity of Gsα due to gain-of-function mutations (R201C/R201H) results in severe architectural and functional derangements of the entire bone/bone marrow organ. While the consequences of gain-of-function mutations of Gsα have been extensively investigated in osteoblasts and in bone marrow osteoprogenitor cells at various differentiation stages, their effect in adipogenically-committed bone marrow stromal cells has remained unaddressed. We generated a mouse model with expression ofGsαR201Cdriven by theAdiponectin(Adq) promoter.Adq-GsαR201Cmice developed a complex combination of metaphyseal, diaphyseal and cortical bone changes. In the metaphysis,GsαR201Ccaused an early phase of bone resorption followed by bone deposition. Metaphyseal bone formation was sustained by cells that were traced byAdq-Creand eventually resulted in a high trabecular bone mass phenotype. In the diaphysis,GsαR201C, in combination with estrogen, triggered the osteogenic activity ofAdq-Cre-targeted perivascular bone marrow stromal cells leading to intramedullary bone formation. Finally, consistent with the previously unnoticed presence ofAdq-Cre-marked pericytes in intraosseous blood vessels,GsαR201Ccaused the development of a lytic phenotype that affected both cortical (increased porosity) and trabecular (tunneling resorption) bone. These results provide the first evidence that theAdq-cell network in the skeleton not only regulates bone resorption but also contributes to bone formation, and that the Gsα/cAMP pathway is a major modulator of both functions.
[11C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer’s disease
Authors: Pascoal Tharick A. , Chamoun Mira , Lax Elad , Wey Hsiao-Ying , Shin Monica , Ng Kok Pin , Kang Min Su , Mathotaarachchi Sulantha , Benedet Andrea L. , Therriault Joseph , Lussier Firoza Z. , Schroeder Frederick A. , DuBois Jonathan M. , Hightower Baileigh G. , Gilbert Tonya M. , Zürcher Nicole R. , Wang Changning , Hopewell Robert , Chakravarty Mallar , Savard Melissa , Thomas Emilie , Mohaddes Sara , Farzin Sarah , Salaciak Alyssa , Tullo Stephanie , Cuello A. Claudio , Soucy Jean-Paul , Massarweh Gassan , Hwang Heungsun , Kobayashi Eliane , Hyman Bradley T. , Dickerson Bradford C. , Guiot Marie-Christine , Szyf Moshe , Gauthier Serge , Hooker Jacob M. , Rosa-Neto Pedro 
Published: July 2022

AbstractAlzheimer’s disease (AD) is characterized by the brain accumulation of amyloid-β and tau proteins. A growing body of literature suggests that epigenetic dysregulations play a role in the interplay of hallmark proteinopathies with neurodegeneration and cognitive impairment. Here, we aim to characterize an epigenetic dysregulation associated with the brain deposition of amyloid-β and tau proteins. Using positron emission tomography (PET) tracers selective for amyloid-β, tau, and class I histone deacetylase (HDAC I isoforms 1–3), we find that HDAC I levels are reduced in patients with AD. HDAC I PET reduction is associated with elevated amyloid-β PET and tau PET concentrations. Notably, HDAC I reduction mediates the deleterious effects of amyloid-β and tau on brain atrophy and cognitive impairment. HDAC I PET reduction is associated with 2-year longitudinal neurodegeneration and cognitive decline. We also find HDAC I reduction in the postmortem brain tissue of patients with AD and in a transgenic rat model expressing human amyloid-β plus tau pathology in the same brain regions identified in vivo using PET. These observations highlight HDAC I reduction as an element associated with AD pathophysiology.
A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours
Authors: Hamed Akram A. , Kunz Daniel J. , El-Hamamy Ibrahim , Trinh Quang M. , Subedar Omar D. , Richards Laura M. , Foltz Warren , Bullivant Garrett , Ware Matthaeus , Vladoiu Maria C. , Zhang Jiao , Raj Antony M. , Pugh Trevor J. , Taylor Michael D. , Teichmann Sarah A. , Stein Lincoln D. , Simons Benjamin D. , Dirks Peter B. 
Published: July 2022

AbstractHuman cerebral cancers are known to contain cell types resembling the varying stages of neural development. However, the basis of this association remains unclear. Here, we map the development of mouse cerebrum across the developmental time-course, from embryonic day 12.5 to postnatal day 365, performing single-cell transcriptomics on >100,000 cells. By comparing this reference atlas to single-cell data from >100 glial tumours of the adult and paediatric human cerebrum, we find that tumour cells have an expression signature that overlaps with temporally restricted, embryonic radial glial precursors (RGPs) and their immediate sublineages. Further, we demonstrate that prenatal transformation of RGPs in a genetic mouse model gives rise to adult cerebral tumours that show an embryonic/juvenile RGP identity. Together, these findings implicate the acquisition of embryonic-like states in the genesis of adult glioma, providing insight into the origins of human glioma, and identifying specific developmental cell types for therapeutic targeting.
Rational design of a topological polymeric solid electrolyte for high-performance all-solid-state alkali metal batteries
Authors: Su Yun , Rong Xiaohui , Gao Ang , Liu Yuan , Li Jianwei , Mao Minglei , Qi Xingguo , Chai Guoliang , Zhang Qinghua , Suo Liumin , Gu Lin , Li Hong , Huang Xuejie , Chen Liquan , Liu Binyuan , Hu Yong-Sheng 
Published: July 2022

AbstractPoly(ethylene oxide)-based solid-state electrolytes are widely considered promising candidates for the next generation of lithium and sodium metal batteries. However, several challenges, including low oxidation resistance and low cation transference number, hinder poly(ethylene oxide)-based electrolytes for broad applications. To circumvent these issues, here, we propose the design, synthesis and application of a fluoropolymer, i.e., poly(2,2,2-trifluoroethyl methacrylate). This polymer, when introduced into a poly(ethylene oxide)-based solid electrolyte, improves the electrochemical window stability and transference number. Via multiple physicochemical and theoretical characterizations, we identify the presence of tailored supramolecular bonds and peculiar morphological structures as the main factors responsible for the improved electrochemical performances. The polymeric solid electrolyte is also investigated in full lithium and sodium metal lab-scale cells. Interestingly, when tested in a single-layer pouch cell configuration in combination with a Li metal negative electrode and a LiMn0.6Fe0.4PO4-based positive electrode, the polymeric solid-state electrolyte enables 200 cycles at 42 mA·g−1 and 70 °C with a stable discharge capacity of approximately 2.5 mAh when an external pressure of 0.28 MPa is applied.
TGFBR1*6A as a modifier of breast cancer risk and progression: advances and future prospects
Authors: Agyemang Kojo , Johansen Allan M. , Barker Grayson W. , Pennison Michael J. , Sheffield Kimberly , Jimenez Hugo , Blackman Carl , Sharma Sambad , Fordjour Patrick A. , Singh Ravi , Cook Katherine L. , Lin Hui-Kuan , Zhang Wei , Lo Hui-Wen , Watabe Kounosuke , Sun Peiqing , Langefeld Carl D. , Pasche Boris 
Published: July 2022

AbstractThere is growing evidence that germline mutations in certain genes influence cancer susceptibility, tumor evolution, as well as clinical outcomes. Identification of a disease-causing genetic variant enables testing and diagnosis of at-risk individuals. For breast cancer, several genes such as BRCA1, BRCA2, PALB2, ATM, and CHEK2 act as high- to moderate-penetrance cancer susceptibility genes. Genotyping of these genes informs genetic risk assessment and counseling, as well as treatment and management decisions in the case of high-penetrance genes. TGFBR1*6A (rs11466445) is a common variant of the TGF-β receptor type I (TGFBR1) that has a global minor allelic frequency (MAF) of 0.051 according to the 1000 Genomes Project Consortium. It is emerging as a high frequency, low penetrance tumor susceptibility allele associated with increased cancer risk among several cancer types. The TGFBR1*6A allele has been associated with increased breast cancer risk in women, OR 1.15 (95% CI 1.01–1.31). Functionally, TGFBR1*6A promotes breast cancer cell proliferation, migration, and invasion through the regulation of the ERK pathway and Rho-GTP activation. This review discusses current findings on the genetic, functional, and mechanistic associations between TGFBR1*6A and breast cancer risk and proposes future directions as it relates to genetic association studies and mechanisms of action for tumor growth, metastasis, and immune suppression.
Validating ground-based aerodynamic levitation surface tension measurements through a study on Al2O3
Authors: Sun Yifan , Duan Guangtao , Yamaji Akifumi , Takatani Tomoya , Muta Hiroaki , Ohishi Yuji 
Published: July 2022

AbstractThe surface tension of a molten sample can be evaluated based on its resonant frequency with various levitation techniques. Under a 1-G condition, the use of levitation forces to counteract gravity will cause the levitated sample’s resonant frequency to differ from that under microgravity. A mathematical relationship to correct for this deviation is not available for a sample levitated with aerodynamic levitation (ADL), which raises issues on the validity of surface tension measurements done with ADL. In this study, we compared the surface tension of molten Al2O3 obtained using the front tracking (FT) simulation method, the drop-bounce method with ADL, and the oscillating drop method with ADL. The drop-bounce method simulates microgravity by allowing the sample to free-fall over a period of tens of milliseconds. Based on the results of this comparison, we determined that the surface tension of molten materials measured with ground-based ADL with the oscillating drop method, calculated using the resonant frequency of the l=2 m=0 mode, only shows a small deviation from that obtained under microgravity.
Phylogeographic inference of Sumatran ranids bearing gastromyzophorous tadpoles with regard to the Pleistocene drainage systems of Sundaland
Authors: Arifin Umilaela , Smart Utpal , Husemann Martin , Hertwig Stefan T. , Smith Eric N. , Iskandar Djoko T. , Haas Alexander 
Published: July 2022

AbstractRivers are known to act as biogeographic barriers in several strictly terrestrial taxa, while possibly serving as conduits of dispersal for freshwater-tolerant or -dependent species. However, the influence of river systems on genetic diversity depends on taxa-specific life history traits as well as other geographic factors. In amphibians, several studies have demonstrated that river systems have only minor influence on their divergence. Here, we assess the role of the paleodrainage systems of the Sunda region (with a focus on the island of Sumatra) in shaping the evolutionary history of two genera of frogs (SumateranaandWijayarana) whose tadpoles are highly dependent on cascading stream habitats. Our phylogenetic results show no clear association between the genetic diversification patterns of both anurans genera and the existence of paleodrainage systems. Time-calibrated phylogenies and biogeographical models suggest that these frogs colonized Sumatra and diversified on the island before the occurrence of the Pleistocene drainage systems. Both genera demonstrate phylogenetic structuring along a north–south geographic axis, the temporal dynamics of which coincide with the geological chronology of proto Sumatran and -Javan volcanic islands. Our results also highlight the chronic underestimation of Sumatran biodiversity and call for more intense sampling efforts on the island.
Ultra-wide-band millimeter-wave generator using spin torque oscillator with strong interlayer exchange couplings
Authors: Kurokawa Yuichiro , Yamada Keisuke , Taniguchi Tomohiro , Horiike Shu , Tanaka Terumitsu , Yuasa Hiromi 
Published: July 2022

AbstractRecent increased development interest in millimeter-wave oscillator devices has necessitated realization of small oscillators with high frequency, wide frequency tunability, and room-temperature operation. Spin-torque oscillators (STOs) are fascinating candidates for such applications because of their nanometer size and suitability for room-temperature operation. However, their oscillation frequency and tunable range are limited to the order of 100 MHz–10 GHz. Here, we propose use of bilinear (J1) and biquadratic (J2) interlayer exchange couplings between ferromagnets in STOs to overcome these problems. The bilinear coupling contributes to oscillation frequency enhancement, whereas the biquadratic coupling facilitates frequency tunability via a current. Using micromagnetic simulation with parameters estimated from a material with small saturation magnetization, for J1 = 0 and J2 =  − 1.0 mJ/m2, respectively, we find that the STO exhibits high frequency from 23 to 576 GHz and that its tunability reaches 61 GHz/(1011 A/m2) for current densities of − 0.5 to − 9.5 × 1011 A/m2. An analytical theory based on the macrospin model is also developed, which exhibits good quantitative agreement with the micromagnetic simulations. These results introduce new possibilities for spintronics applications in high-frequency devices such as next-generation mobile communications.
Kynurenine metabolites predict survival in pulmonary arterial hypertension: A role for IL-6/IL-6Rα
Authors: Cai Zongye , Tian Siyu , Klein Theo , Tu Ly , Geenen Laurie W. , Koudstaal Thomas , van den Bosch Annemien E. , de Rijke Yolanda B. , Reiss Irwin K. M. , Boersma Eric , van der Ley Claude , Van Faassen Martijn , Kema Ido , Duncker Dirk J. , Boomars Karin A. , Tran-Lundmark Karin , Guignabert Christophe , Merkus Daphne 
Published: July 2022

AbstractActivation of the kynurenine pathway (KP) has been reported in patients with pulmonary arterial hypertension (PAH) undergoing PAH therapy. We aimed to determine KP-metabolism in treatment-naïve PAH patients, investigate its prognostic values, evaluate the effect of PAH therapy on KP-metabolites and identify cytokines responsible for altered KP-metabolism. KP-metabolite levels were determined in plasma from PAH patients (median follow-up 42 months) and in rats with monocrotaline- and Sugen/hypoxia-induced PH. Blood sampling of PAH patients was performed at the time of diagnosis, six months and one year after PAH therapy. KP activation with lower tryptophan, higher kynurenine (Kyn), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), kynurenic acid (KA), and anthranilic acid was observed in treatment-naïve PAH patients compared with controls. A similar KP-metabolite profile was observed in monocrotaline, but not Sugen/hypoxia-induced PAH. Human lung primary cells (microvascular endothelial cells, pulmonary artery smooth muscle cells, and fibroblasts) were exposed to different cytokines in vitro. Following exposure to interleukin-6 (IL-6)/IL-6 receptor α (IL-6Rα) complex, all cell types exhibit a similar KP-metabolite profile as observed in PAH patients. PAH therapy partially normalized this profile in survivors after one year. Increased KP-metabolites correlated with higher pulmonary vascular resistance, shorter six-minute walking distance, and worse functional class. High levels of Kyn, 3-HK, QA, and KA measured at the latest time-point were associated with worse long-term survival. KP-metabolism was activated in treatment-naïve PAH patients, likely mediated through IL-6/IL-6Rα signaling. KP-metabolites predict response to PAH therapy and survival of PAH patients.
Interrupted time series analysis for the impact of integrated medical insurance on direct hospitalization expense of catastrophic illness
Authors: Niu Li , Song Qiuhe , Liu Yan , Wang Xin 
Published: July 2022

AbstractIn 2016, China initiated the merge of the urban resident basic medical insurance scheme and new rural cooperative medical scheme into one unified health insurance scheme: the urban and rural resident basic medical insurance. This study investigates the impact of integrated insurance on the direct hospitalization cost of inpatients with catastrophic illnesses. An interrupted time series analysis was conducted based on a sample of 6174 inpatients with catastrophic illness from January 2014 to December 2018. The factors surveyed included per capita total inpatient expense, out-of-pocket expense, and reimbursement ratio. Univariate analysis indicated that after the implementation of the unified urban and rural medical insurance, the reimbursed expense increased from 9398 to 13,842 Yuan (P < 0.001), average reimbursement ratio increased from 0.57 to 0.59 (P < 0.05). Expenses on both western and traditional medicines increased, although the proportion of medicine expense decreased after the integration. Interrupted time series analysis showed that per capita total inpatient expense and per capita out-of-pocket expense increased but showed a gradually decreasing trend after the integration. After the integration of urban and rural medical insurance, the average reimbursement ratio increased slightly, which had limited effect on the alleviation of patients’ financial burden. Furthermore, the integration effect on inpatient expense is offset by increased out-of-pocket medical expense due to suspected supplier-induced demand.
A study of high neuroticism in long-term survivors of childhood, adolescence, and young adult cancers
Authors: Dahl Alv A. , Kiserud Cecilie Essholt , Fosså Sophie D. , Loge Jon Håvard , Reinertsen Kristin Valborg , Ruud Ellen , Lie Hanne C. 
Published: July 2022

AbstractNeuroticism is a basic personality trait concerning negative feelings under stressful conditions. Our purpose was to examine the rate of high neuroticism and factors associated with high neuroticism in long-term (≥ 5 years) survivors of childhood, adolescent, and young adult cancer (CAYACSs). Norwegian CAYACSs aged 0–39 years when diagnosed and treated between 1985 and 2009 for cancer in childhood/adolescence (0–18 years), or as young adults (19–39 years) and alive in 2015 were mailed a questionnaire. Data from 1629 CAYACSs (481 children/adolescents and 1148 young adults) were analyzed. High neuroticism was found in 44% of survivors of childhood/adolescent cancers versus 34% in survivors of young adult cancer (p < 0.001). The rate of high neuroticism in female CAYACSs was 40% and in males 30% (p < 0.001). The corresponding difference between male survivor group was non-significant. In multivariable analysis, young age at survey, more adverse effects, poor self-rated health, female sex, chronic fatigue, and increased depression remained significantly associated with high neuroticism. Cancer treatment, comorbidity, and lifestyle were significant in bivariate analyses. Cancer at earlier age could increase the risk of high neuroticism among adult survivors. Screening for neuroticism could identify CAYACSs at risk for experiencing multiple health concerns and needing special follow-up attention.