bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I dose-escalation study of F14512, a polyamine-vectorized topoisomerase II inhibitor, in patients with platinum-refractory or resistant ovarian cancer
Authors: Leary Alexandra , Le Tourneau Christophe , Varga Andrea , Sablin Marie-Paule , Gomez-Roca Carlos , Guilbaud Nicolas , Petain Aurelie , Pavlyuk Mariya , Delord Jean-Pierre 
Published: December 2018

Summary
Purpose To determine the maximum tolerated dose (MTD) of F14512, a topoisomerase II inhibitor designed to target cancer cells through the polyamine transport system, (three-hour daily infusion given for 3 consecutive days every 3 weeks) in platinum-refractory or resistant ovarian cancer. Other objectives were safety, pharmacokinetics (PK), PK/pharmacodynamics relationship, and efficacy. Methods This was an open-label, dose-escalation, multicenter phase I study. Results Eleven patients were enrolled and were treated at dose levels (DLs) of 10 and 5 mg/m2/day. All patients received the 3 injections per cycle as per study protocol (median, 1 cycle (Ferlay et al. Int J Cancer 136:E359–386, 2015; Siegel et al. CA Cancer J Clin 65:5–29, 2015; Oronsky et al. Med Oncol 34:103, 2017; Barret et al. Cancer Res 68:9845–9853, 2008; Ballot et al. Apoptosis 17:364–376, 2012; Brel et al. Biochem Pharmacol 82:1843–1852, 2011; Gentry et al. Biochemistry 50:3240–3249, 2011; Kruczynski et al. Investig New Drugs 29:9–21, 2011; Chelouah et al. PLoS One 6:e23597, 2011)) with no dose reductions. At DL 10 mg/m2/day, 6 dose-limiting toxicities (DLTs) were reported (3/4 evaluable patients: 2 grade 3 febrile neutropenia, 1 grade 4 neutropenia lasting at least 7 days, 1 grade 3 nausea, 1 decreased appetite, and 1 grade 3 asthenia). At dose 5 mg/m2/day, 2 DLTs were reported (2/6 treated patients: 2 grade 3 febrile neutropenia). Both DLs were defined as MTD. Stable disease was reported as best overall response in 2 (40%) patients having both received 9 cycles, one at each DL. 90.9% of patients experienced grade 4 neutropenia, but for only one (9.1%) it was reported as a serious adverse event. Conclusion Although there was some encouraging efficacy signal, grade 4 neutropenia led to complications and it was
decided to stop the study. A DL below 5 mg/m2/day was not tested as this would not allow reaching the minimum serum concentration needed for the pharmacological activity of the drug.
Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need
Authors: Babulal Ganesh M. , Quiroz Yakeel T. , Albensi Benedict C. , Arenaza‐Urquijo Eider , Astell Arlene J. , Babiloni Claudio , Bahar‐Fuchs Alex , Bell Joanne , Bowman Gene L. , Brickman Adam M. , Chételat Gaël , Ciro Carrie , Cohen Ann D. , Dilworth‐Anderson Peggye , Dodge Hiroko H. , Dreux Simone , Edland Steven , Esbensen Anna , Evered Lisbeth , Ewers Michael , Fargo Keith N. , Fortea Juan , Gonzalez Hector , Gustafson Deborah R. , Head Elizabeth , Hendrix James A. , Hofer Scott M. , Johnson Leigh A. , Jutten Roos , Kilborn Kerry , Lanctôt Krista L. , Manly Jennifer J. , Martins Ralph N. , Mielke Michelle M. , Morris Martha Clare , Murray Melissa E. , Oh Esther S. , Parra Mario A. , Rissman Robert A. , Roe Catherine M. , Santos Octavio A. , Scarmeas Nikolaos , Schneider Lon S. , Schupf Nicole , Sikkes Sietske , Snyder Heather M. , Sohrabi Hamid R. , Stern Yaakov , Strydom Andre , Tang Yi , Terrera Graciela Muniz , Teunissen Charlotte , Melo van Lent Debora , Weinborn Michael , Wesselman Linda , Wilcock Donna M. , Zetterberg Henrik , O'Bryant Sid E. ,   on behalf of the International Society to Advance Alzheimer's Research and Treatment, Alzheimer's Association
Published: December 2018

AbstractAlzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross‐PIA white paper that provides both a concise “state‐of‐the‐science” report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.
On the Maximization of Joint Velocities and Generalized Reactions in the Workspace and Singularity Analysis of Parallel Mechanisms
Authors: Laryushkin Pavel , Glazunov Victor , Erastova Ksenia 
Published: December 2018

SummaryAn approach for calculating the maximum possible absolute values of joint velocities or generalized reactions in a leg of a parallel mechanism has been considered in this paper. The Jacobian analysis and the Screw theory-based methods have been used to acquire the result. These values are calculated for the “worst” directions of the external load or end-effector’s velocity for each leg. The feasibility of using these parameters as the measures of closeness to different types of parallel mechanism singularity is discussed. Further, how this approach is related to the state-of-the-art methods has been illustrated. The key aspect of the discussed approach is that the normalization of vectors or screws is carried out separately for angular and linear components. One possible advantage of such an approach is that it deals only with the kinematic and statics of the mechanism while still providing physically meaningful and practically applicable measures. Case studies of a 3-Degrees Of Freedom translational parallel mechanism and a planar parallel mechanism are presented for illustration and comparison.
Depletion and Traveling Ionospheric Disturbances Generated by Two Launches of China's Long March 4B Rocket
Authors: Liu Haitao , Ding Feng , Yue Xinan , Zhao Biqiang , Song Qian , Wan Weixing , Ning Baiqi , Zhang Keke 
Published: December 2018

AbstractUsing total electron content (TEC) data from 902 global navigation satellite system stations over China, we analyzed the ionospheric responses following two similar launches of the Long March 4B from Taiyuan, China, that is, China‐Brazil Earth Resources Satellite 3 launched on 9 December 2013 and China‐Brazil Earth Resources Satellite 4 launched on 7 December 2014. By adopting a method that can detect TEC depletion effectively, filtered TEC series, and built two‐dimensional disturbances map, we found that the ionospheric disturbances of these two launches were almost the same. We identified three types of disturbances following both launches: depletions, shock wave‐related traveling ionospheric disturbances (TIDs), and acoustic wave‐related circle TIDs. The buildup time of depletion was influenced by the amount of exhaust expelled into the ionosphere with an amplitude of ∼12 TEC unit (TECU; 1 TECU = 1016 el/m2). After the electron depletion was formed, it drifted westward for approximately 300 km. The shock wave‐related TIDs can only be observed near the trajectory and reflect the acceleration of the rockets with an amplitude of ∼0.6 TECU. The acoustic wave‐related circle TIDs were observed at the southeast of the launch site. From our observations, this type of TID includes three groups of wave trains, and the speed and period are ∼900 m/s and ∼3.8 min, respectively. The amplitudes of the three groups of TIDs are ∼0.065, ∼0.045, and ∼0.02 TECU.
The Role of Heart Rate Variability Biofeedback in Pediatric Chronic Pain Rehabilitation: A Case Series Design
Authors: Fahrenkamp Amy , Benore Ethan 
Published: December 2018

Biofeedback is 1 form of complementary therapy commonly used to treat pediatric chronic pain. Given the limited research in biofeedback treatment outcomes with youth experiencing chronic pain, the present study sought to initially examine the potential for heart rate variability (HRV) biofeedback to support self-regulation training for adolescents participating in a chronic pain rehabilitation program. Using a case series design, this study examined changes in HRV and respiration rate for 4 adolescents with chronic pain. Adolescents completed an initial assessment followed by 3–4 biofeedback training sessions. The Nexus 10 biofeedback system (BioTrace+ software) was used to obtain respiration rate and HRV low-frequency percentage. Visual inspection of plotted graphs from adolescents’ HRV biofeedback training demonstrated (a) improved cardiopulmonary functioning across sessions during active training, (b) changed cardiopulmonary functioning across sessions during baseline assessment, and (c) improved functioning without active feedback, suggesting self-regulation of cardiopulmonary functioning. Adolescents using a brief protocol of HRV biofeedback training demonstrated expected changes in cardiopulmonary functioning and self-regulation. Similar to findings in adults, HRV biofeedback yields promise as an intervention to treat children with chronic pain and comorbid symptoms. However, because this is an initial study, additional research with more rigorous methodology is needed to further support the benefit of HRV biofeedback in modifying physiological awareness and self-regulation and the connection of this self-regulation with clinical outcomes. Future clinical research should build on these initial findings to develop and test biofeedback protocols to treat chronic pain in children. Implications for Impact Statement Findings from this case series design showed initial benefits in increasing adolescents’ physiological self-regulation skills. Providers may draw clinical applications from these self-regulation techniques within and outside of a biofeedback context to teach increased awareness, control, and generalization of self-regulatory skills to cope with negative experiences.
IgSF9b regulates anxiety behaviors through effects on centromedial amygdala inhibitory synapses
Authors: Babaev Olga , Cruces-Solis Hugo , Piletti Chatain Carolina , Hammer Matthieu , Wenger Sally , Ali Heba , Karalis Nikolaos , de Hoz Livia , Schlüter Oliver M. , Yanagawa Yuchio , Ehrenreich Hannelore , Taschenberger Holger , Brose Nils , Krueger-Burg Dilja 
Published: December 2018

AbstractAbnormalities in synaptic inhibition play a critical role in psychiatric disorders, and accordingly, it is essential to understand the molecular mechanisms linking components of the inhibitory postsynapse to psychiatrically relevant neural circuits and behaviors. Here we study the role of IgSF9b, an adhesion protein that has been associated with affective disorders, in the amygdala anxiety circuitry. We show that deletion of IgSF9b normalizes anxiety-related behaviors and neural processing in mice lacking the synapse organizer Neuroligin-2 (Nlgn2), which was proposed to complex with IgSF9b. This normalization occurs through differential effects of Nlgn2 and IgSF9b at inhibitory synapses in the basal and centromedial amygdala (CeM), respectively. Moreover, deletion of IgSF9b in the CeM of adult Nlgn2 knockout mice has a prominent anxiolytic effect. Our data place IgSF9b as a key regulator of inhibition in the amygdala and indicate that IgSF9b-expressing synapses in the CeM may represent a target for anxiolytic therapies.
Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs
Authors: Ganuza Miguel , Chabot Ashley , Tang Xing , Bi Wenjian , Natarajan Sivaraman , Carter Robert , Gawad Charles , Kang Guolian , Cheng Yong , McKinney-Freeman Shannon 
Published: December 2018

AbstractThe embryonic site of definitive hematopoietic stem cell (dHSC) origination has been debated for decades. Although an intra-embryonic origin is well supported, the yolk sac (YS) contribution to adult hematopoiesis remains controversial. The same developmental origin makes it difficult to identify specific markers that discern between an intraembryonic versus YS-origin using a lineage trace approach. Additionally, the highly migratory nature of blood cells and the inability of pre-circulatory embryonic cells (i.e., 5–7 somite pairs (sp)) to robustly engraft in transplantation, even after culture, has precluded scientists from properly answering these questions. Here we report robust, multi-lineage and serially transplantable dHSC activity from cultured 2–7sp murine embryonic explants (Em-Ex). dHSC are undetectable in 2–7sp YS explants. Additionally, the engraftment from Em-Ex is confined to an emerging CD31+CD45+c-Kit+CD41−population. In sum, our work supports a model in which the embryo, not the YS, is the major source of lifelong definitive hematopoiesis.
Author Correction: Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors
Authors: Cheng Jiqiu , Demeulemeester Jonas , Wedge David C. , Vollan Hans Kristian M. , Pitt Jason J. , Russnes Hege G. , Pandey Bina P. , Nilsen Gro , Nord Silje , Bignell Graham R. , White Kevin P. , Børresen-Dale Anne-Lise , Campbell Peter J. , Kristensen Vessela N. , Stratton Michael R. , Lingjærde Ole Christian , Moreau Yves , Van Loo Peter 
Published: December 2018

The original version of this Article contained an error in the author affiliations. The affiliation of Kevin P. White with Tempus Labs, Inc., Chicago, IL, USA was inadvertently omitted.This has now been corrected in both the PDF and HTML versions of the Article.
The ASCIZ-DYNLL1 axis promotes 53BP1-dependent non-homologous end joining and PARP inhibitor sensitivity
Authors: Becker Jordan R. , Cuella-Martin Raquel , Barazas Marco , Liu Rui , Oliveira Catarina , Oliver Antony W. , Bilham Kirstin , Holt Abbey B. , Blackford Andrew N. , Heierhorst Jörg , Jonkers Jos , Rottenberg Sven , Chapman J. Ross 
Published: December 2018

Abstract53BP1 controls a specialized non-homologous end joining (NHEJ) pathway that is essential for adaptive immunity, yet oncogenic in BRCA1 mutant cancers. Intra-chromosomal DNA double-strand break (DSB) joining events during immunoglobulin class switch recombination (CSR) require 53BP1. However, in BRCA1 mutant cells, 53BP1 blocks homologous recombination (HR) and promotes toxic NHEJ, resulting in genomic instability. Here, we identify the protein dimerization hub—DYNLL1—as an organizer of multimeric 53BP1 complexes. DYNLL1 binding stimulates 53BP1 oligomerization, and promotes 53BP1’s recruitment to, and interaction with, DSB-associated chromatin. Consequently, DYNLL1 regulates 53BP1-dependent NHEJ: CSR is compromised upon deletion of Dynll1 or its transcriptional regulator Asciz, or by mutation of DYNLL1 binding motifs in 53BP1; furthermore, Brca1 mutant cells and tumours are rendered resistant to poly-ADP ribose polymerase (PARP) inhibitor treatments upon deletion of Dynll1 or Asciz. Thus, our results reveal a mechanism that regulates 53BP1-dependent NHEJ and the therapeutic response of BRCA1-deficient cancers.
Distribution and correlation between phylogeny and functional traits of cowpea (Vigna unguiculata L. Walp.)-nodulating microsymbionts from Ghana and South Africa
Authors: Mohammed Mustapha , Jaiswal Sanjay K. , Dakora Felix D. 
Published: December 2018

AbstractCowpea (Vigna unguiculata L. Walp.) is indigenous to Africa, and highly valued for its N2-fixing trait and the nutritional attributes of its grain and leaves. The species’ ability to establish effective symbiosis with diverse rhizobial populations gives it survival and growth advantage in N-limited environments. To explore the functional diversity and phylogenetic positions of rhizobia nodulating cowpea in Africa, nodules were collected from various cowpea varieties grown in soils from the Guinea savanna and Sudano-sahelian agroecologies of Northern Ghana, and from the lowveld and middleveld areas of Mpumalanga Province in South Africa. Box-PCR profiling and multilocus sequence analysis revealed the presence of diverse microsymbionts responsible for cowpea nodulation across the study sites. BOX-PCR amplifications yielded variable band sizes, ranging from 618 bp to 5354 bp, which placed the isolates in six major clusters (Cluster A–F). Phylogenetic analysis based on 16S rRNA, atpD, glnII, gyrB, rpoB, nifH and nodC genes revealed the presence of diverse Bradyrhizobium sp. closely related to Bradyrhizobium daqingense, Bradyrhizobium subterraneum, Bradyrhizobium yuanmingense, Bradyrhizobium embrapense, Bradyrhizobium pachyrhizi, Bradyrhizobium elkanii and novel Bradyrhizobium species in the soils studied, a finding that could be attributed to the unique edapho-climatic conditions of the contrasting environments. The test isolates exhibited distinct symbiotic efficiencies, and also induced variable (p ≤ 0.001) photosynthetic rates, leaf transpiration, total chlorophyll and shoot biomass accumulation on cowpea (their homologous host). Canonical correspondence analysis showed that the distribution of these microsymbionts was influenced by the concentrations of macro- and micronutrients in soils. The pairwise genetic distances derived from phylogenies and nodule functioning showed significant (p < 0.05) correlation, which suggests that local environmental factors played a major role in the cowpea-Bradyrhizobium symbiosis.
Cochlear Implantation in Postlingually Deaf Adults is Time-sensitive Towards Positive Outcome: Prediction using Advanced Machine Learning Techniques
Authors: Kim Hosung , Kang Woo Seok , Park Hong Ju , Lee Jee Yeon , Park Jun Woo , Kim Yehree , Seo Ji Won , Kwak Min Young , Kang Byung Chul , Yang Chan Joo , Duffy Ben A. , Cho Young Sang , Lee Sang-Youp , Suh Myung Whan , Moon Il Joon , Ahn Joong Ho , Cho Yang-Sun , Oh Seung Ha , Chung Jong Woo 
Published: December 2018

AbstractGiven our aging society and the prevalence of age-related hearing loss that often develops during adulthood, hearing loss is a common public health issue affecting almost all older adults. Moderate-to-moderately severe hearing loss can usually be corrected with hearing aids; however, severe-to-profound hearing loss often requires a cochlear implant (CI). However, post-operative CI results vary, and the performance of the previous prediction models is limited, indicating that a new approach is needed. For postlingually deaf adults (n de120) who received CI with full insertion, we predicted CI outcomes using a Random-Forest Regression (RFR) model and investigated the effect of preoperative factors on CI outcomes. Postoperative word recognition scores (WRS) served as the dependent variable to predict. Predictors included duration of deafness (DoD), age at CI operation (ageCI), duration of hearing-aid use (DoHA), preoperative hearing threshold and sentence recognition score. Prediction accuracy was evaluated using mean absolute error (MAE) and Pearson’s correlation coefficient r between the true WRS and predicted WRS. The fitting using a linear model resulted in prediction of WRS with r = 0.7 and MAE = 15.6 ± 9. RFR outperformed the linear model (r = 0.96, MAE = 6.1 ± 4.7, p < 0.00001). Cross-hospital data validation showed reliable performance using RFR (r = 0.91, MAE = 9.6 ± 5.2). The contribution of DoD to prediction was the highest (MAE increase when omitted: 14.8), followed by ageCI (8.9) and DoHA (7.5). After CI, patients with DoD < 10 years presented better WRSs and smaller variations (p < 0.01) than those with longer DoD. Better WRS was also explained by younger age at CI and longer-term DoHA. Machine learning demonstrated a robust prediction performance for CI outcomes in postlingually deaf adults across different institutes, providing a reference value for counseling patients considering CI. Health care providers should be aware that the patients with severe-to-profound hearing loss who cannot have benefit from hearing aids need to proceed with CI as soon as possible and should continue using hearing aids until after CI operation.
Induction of Human T-cell and Cytokine Responses Following Vaccination with a Novel Influenza Vaccine
Authors: Skibinski David A. G. , Jones Leigh Ann , Zhu Yuan O. , Xue Lin Wu , Au Bijin , Lee Bernett , Naim Ahmad Nazri Mohamed , Lee Audrey , Kaliaperumal Nivashini , Low Jenny G. H. , Lee Lawrence S. , Poidinger Michael , Saudan Philippe , Bachmann Martin , Ooi Eng Eong , Hanson Brendon J. , Novotny-Diermayr Veronica , Matter Alex , Fairhurst Anna-Marie , Hibberd Martin L. , Connolly John E. 
Published: December 2018

AbstractCell mediated immunity plays a vital role in defense against influenza infection in humans. Less is known about the role of vaccine-induced cell mediated immunity and the cytokine responses elicited. We measured CD4+ and CD8+ T-cell reactivity in human subjects following vaccination with licensed trivalent influenza vaccine and a novel virus-like particle based vaccine. We detected influenza-specific CD4+ T-cell responses following vaccination with the licensed trivalent influenza vaccine and found that these correlated with antibody measurements. Administration of the novel virus-like particle based vaccine elicited influenza-specific CD4+ and CD8+ T-cell responses and the induction of the cytokines IFN-γ, IL-17A, IL17F, IL-5, IL-13, IL-9, IL-10 and IL-21. Pre-existing cytokine responses influenced the profile of the cytokine response elicited by vaccination. In a subset of individuals the VLP vaccine changed pre-vaccination production of type 2 cytokines such as IL-5 and IL-13 to a post-vaccination type 1 cytokine signature characterized by IFN-γ. A transcriptional signature to vaccination was found to correlate with antibody titer, IFN-γ production by T-cells and expression of a putative RNA helicase, DDX17, on the surface of immune cells.
Different pro-angiogenic potential of γ-irradiated PBMC-derived secretome and its subfractions
Authors: Wagner Tanja , Traxler Denise , Simader Elisabeth , Beer Lucian , Narzt Marie-Sophie , Gruber Florian , Madlener Sibylle , Laggner Maria , Erb Michael , Vorstandlechner Vera , Gugerell Alfred , Radtke Christine , Gnecchi Massimiliano , Peterbauer Anja , Gschwandtner Maria , Tschachler Erwin , Keibl Claudia , Slezak Paul , Ankersmit Hendrik J. , Mildner Michael 
Published: December 2018

AbstractSecretomes from various cell sources exert strong regenerative activities on numerous organs, including the skin. Although secretomes consist of many diverse components, a growing body of evidence suggests that small extracellular vesicles (EVs) account for their regenerative capacity. We previously demonstrated that the secretome of γ-irradiated peripheral blood mononuclear cells (PBMCs) exhibits wound healing capacity. Therefore, we sought to dissect the molecular composition of EVs present in the secretome and compared wound healing-related activities of these EVs to other subfractions of the secretome and the fully supplemented secretome (MNCaposec). Compared to EVs derived from non-irradiated PBMCs, γ-irradiation significantly increased the size and number and changed the composition of released EVs. Detailed characterization of the molecular components of EVs, i.e. miRNA, proteins, and lipids, derived from irradiated PBMCs revealed a strong association with regenerative processes. Reporter gene assays and aortic ring sprouting assays revealed diminished activity of the subfractions compared to MNCaposec. In addition, we showed that MNCaposec accelerated wound closure in a diabetic mouse model. Taken together, our results suggest that secretome-based wound healing represents a promising new therapeutic avenue, and strongly recommend using the complete secretome instead of purified subfractions, such as EVs, to exploit its full regenerative capacity.