bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of SIRT6 by DNA hypomethylating agents and clinical consequences on combination therapy in leukemia
Authors: Carraway Hetty E. , Malkaram Sridhar A. , Cen Yana , Shatnawi Aymen , Fan Jun , Ali Hamdy E. A. , Abd Elmageed Zakaria Y. , Buttolph Thomm , Denvir James , Primerano Donald A. , Fandy Tamer E. 
Published: June 2020

AbstractThe FDA-approved DNA hypomethylating agents (DHAs) like 5-azacytidine (5AC) and decitabine (DAC) demonstrate efficacy in the treatment of hematologic malignancies. Despite previous reports that showed histone acetylation changes upon using these agents, the exact mechanism underpinning these changes is unknown. In this study, we investigated the relative potency of the nucleoside analogs and non-nucleoside analogs DHAs on DNA methylation reversal using DNA pyrosequencing. Additionally, we screened their effect on the enzymatic activity of the histone deacetylase sirtuin family (SIRT1, SIRT2, SIRT3, SIRT5 and SIRT6) using both recombinant enzymes and nuclear lysates from leukemia cells. The nucleoside analogs (DAC, 5AC and zebularine) were the most potent DHAs and increased the enzymatic activity of SIRT6 without showing any significant increase in other sirtuin isoforms. ChIP-Seq analysis of bone marrow cells derived from six acute myeloid leukemia (AML) patients and treated with the nucleoside analog DAC induced genome-wide acetylation changes in H3K9, the physiological substrate for SIRT6. Data pooling from the six patients showed significant acetylation changes in 187 gene loci at different chromosomal regions including promoters, coding exons, introns and distal intergenic regions. Signaling pathway analysis showed that H3K9 acetylation changes are linked to AML-relevant signaling pathways like EGF/EGFR and Wnt/Hedgehog/Notch. To our knowledge, this is the first report to identify the nucleoside analogs DHAs as activators of SIRT6. Our findings provide a rationale against the combination of the nucleoside analogs DHAs with SIRT6 inhibitors or chemotherapeutic agents in AML due to the role of SIRT6 in maintaining genome integrity and DNA repair.
A machine learning-based prognostic predictor for stage III colon cancer
Authors: Jiang Dan , Liao Junhua , Duan Haihan , Wu Qingbin , Owen Gemma , Shu Chang , Chen Liangyin , He Yanjun , Wu Ziqian , He Du , Zhang Wenyan , Wang Ziqiang 
Published: June 2020

AbstractLimited biomarkers have been identified as prognostic predictors for stage III colon cancer. To combat this shortfall, we developed a computer-aided approach which combing convolutional neural network with machine classifier to predict the prognosis of stage III colon cancer from routinely haematoxylin and eosin (H&E) stained tissue slides. We trained the model by using 101 cancers from West China Hospital (WCH). The predictive effectivity of the model was validated by using 67 cancers from WCH and 47 cancers from The Cancer Genome Atlas Colon Adenocarcinoma database. The selected model (Gradient Boosting-Colon) provided a hazard ratio (HR) for high- vs. low-risk recurrence of 8.976 (95% confidence interval (CI), 2.824–28.528; P, 0.000), and 10.273 (95% CI, 2.177–48.472; P, 0.003) in the two test groups, from the multivariate Cox proportional hazards analysis. It gave a HR value of 10.687(95% CI, 2.908–39.272; P, 0.001) and 5.033 (95% CI,1.792–14.132; P, 0.002) for the poor vs. good prognosis groups. Gradient Boosting-Colon is an independent machine prognostic predictor which allows stratification of stage III colon cancer into high- and low-risk recurrence groups, and poor and good prognosis groups directly from the H&E tissue slides. Our findings could provide crucial information to aid treatment planning during stage III colon cancer.
Growth Factor Midkine Aggravates Pulmonary Arterial Hypertension via Surface Nucleolin
Authors: Kinoshita Daisuke , Shishido Tetsuro , Takahashi Tetsuya , Yokoyama Miyuki , Sugai Takayuki , Watanabe Ken , Tamura Harutoshi , Nishiyama Satoshi , Takahashi Hiroki , Arimoto Takanori , Miyamoto Takuya , Watanabe Tetsu , Kishida Satoshi , Kadomatsu Kenji , Abe Jun-ichi , Takeishi Yasuchika , Konta Tsuneo , Kubota Isao , Watanabe Masafumi 
Published: June 2020

AbstractPulmonary arterial hypertension (PAH) is a progressive fatal disease caused by pulmonary arterial remodeling. Midkine regulates cell proliferation and migration, and it is induced by hypoxia, but its roles in pulmonary arterial remodeling remain unclear. Serum midkine levels were significantly increased in PAH patients compared with control patients. Midkine expression was increased in lungs and sera of hypoxia-induced PAH mice. Hypoxia-induced pulmonary arterial remodeling and right ventricular hypertrophy were attenuated in midkine-knockout mice. Midkine-induced proliferation and migration of pulmonary arterial smooth muscle cells (PASMC) and epidermal growth factor receptor (EGFR) signaling were significantly increased under hypoxia, which also induced cell-surface translocation of nucleolin. Nucleolin siRNA treatment suppressed midkine-induced EGFR activation in vitro, and nucleolin inhibitor AS1411 suppressed proliferation and migration of PASMC induced by midkine. Furthermore, AS1411 significantly prevented the development of PAH in Sugen hypoxia rat model. Midkine plays a crucial role in PAH development through interaction with surface nucleolin. These data define a role for midkine in PAH development and suggest midkine-nucleolin-EGFR axis as a novel therapeutic target for PAH.
Enhanced spinal neuronal responses as a mechanism for increased number and size of active acupoints in visceral hyperalgesia
Authors: Fan Yu , Ryu Yeonhee , Zhao Rongjie , Bills Kyle B. , Steffensen Scott C. , Yang Chae Ha , Kim Hee Young 
Published: June 2020

AbstractAcupuncture has been used to treat a variety of illness and involves the insertion and manipulation of needles into specific points on the body (termed “acupoints”). It has been suggested that acupoints are not merely discrete, static points, but can be dynamically changed according to the pathological state of internal organs. We investigated in a rat model of mustard oil (MO)-induced visceral hyperalgesia whether the number and size of acupoints were modified according to the severity of the colonic pain, and whether the changes were associated with enhanced activity of the spinal dorsal horn. In MO-treated rats, acupoints showing neurogenic inflammation (termed “neurogenic spots” or Neuro-Sps) were found both bilaterally and unilaterally on the leg. The number and size of these acupoints increased along with increasing doses of MO. Electroacupuncture of the acupoints generated analgesic effects on MO-induced visceral hypersensitivity. The MO-treated rats showed an increase in c-Fos expression in spinal dorsal horn neurons and displayed increased evoked activity and a prolonged after-discharge in spinal wide dynamic response (WDR) neurons in response to colorectal distension. Increased number and size of neurogenic inflammatory acupoints following MO treatment were reduced by inhibiting AMPA and NMDA receptors in the spinal cord. Our findings suggest that acupoints demonstrate increased number and size along with severity of visceral pain, which may be associated with enhanced neuronal responses in spinal dorsal horn neurons.
Retinal Oxygen Delivery, Metabolism, and Extraction Fraction during Long-Term Bilateral Common Carotid Artery Occlusion in Rats
Authors: Leahy Sophie , Farzad Shayan , Blair Norman P. , Shahidi Mahnaz 
Published: June 2020

AbstractRetinal functional, biochemical, and anatomical changes have been previously reported in long-term experimental permanent bilateral common carotid artery occlusion (BCCAO). The purpose of the current study was to investigate progressive reductions in retinal oxygen metabolism (MO2) due to inadequate compensation by oxygen delivery (DO2) and extraction fraction (OEF) after BCCAO. Twenty-nine rats were subjected to BCCAO and were imaged after 3 hours, 3 days, 7 days, or 14 days. Six rats underwent a sham procedure. Phosphorescence lifetime and blood flow imaging were performed in both eyes to measure retinal oxygen contents and total retinal blood flow, respectively. DO2, MO2, and OEF were calculated from these measurements. Compared to the sham group, DO2 and MO2 were reduced after all BCCAO durations. OEF was increased after 3 hours and 3 days of BCCAO, but was not different from the sham group after 7 and 14 days. Between 3 and 7 days of BCCAO, DO2 increased, OEF decreased, and there was no significant difference in MO2. These findings may be useful to understand the pathophysiology of retinal ischemia.
Impact of chronic HCV treatment on quality of life of patients with metabolic disorders in context of immunological disturbances
Authors: Kierepa Agata , Witkowska Aleksandra , Kaczmarek Mariusz , Książek Krzysztof , Mikuła-Pietrasik Justyna , Żeromski Jan , Kowala-Piaskowska Arleta , Mozer-Lisewska Iwona 
Published: June 2020

AbstractChronic viral hepatitis C (CHC) and its complications have a negative effect on patient’s quality of life. We evaluated the impact of a successful interferon-free treatment on the quality of life of patients with obesity and metabolic disorders in the context of immunological disturbances. Twenty overweight or obese (BMI > 25) patients with CHC were tested before the therapy and after a successful treatment regimen. After the therapy, patient’s emotional well-being improved (p = 0.02), while physical well-being remained unchanged. There was a decrease of patient’s liver fibrosis and an increase of steatosis along with body mass. Among HCV-infected individuals, the expression of toll-like receptor 3 (TLR3) on lymphocytes was higher than in the control group (p = 0.03), but it decreased (p = 0.001) after the treatment. There was also a decrease of the intensity of immunofluorescence of FoxP3+ after the treatment (p = 0.04). Our study showed an improvement in mental aspects of patient’s quality of life after the treatment. Unfortunately, probably due to rapid immunological changes, patient’s BMI, serum cholesterol levels and hepatic steatosis have a tendency to increase and may lead to cardiovascular and other complications, like hepatocellular carcinoma.
A theoretical investigation on reciprocity-inspired wide-angle spectrally-selective THz absorbers augmented by anisotropic metamaterials
Authors: Mohammadi Mansoureh , Rajabalipanah Hamid , Abdolali Ali 
Published: June 2020

AbstractIn this paper, a theoretical framework relying on the reciprocity theorem is proposed to accurately design a spectrally-selective THz superstrate-loaded metamaterial absorber (SLMA) exhibiting wide-angle feature. By leveraging high-order Floquet harmonics in a generalized transmission line model characterizing the conventional metamaterial absorbers (MAs), it is demonstrated that MAs suffer from impedance mismatch, especially at near grazing angles. From an impedance matching viewpoint, this major challenge is tackled in this paper via two different designs, exploiting a magneto-electric anisotropic Huygens' metamaterial and a multilayer dielectric structure at a certain distance over the MA plane. The numerical results corroborate well the theoretical predictions, elucidating that the proposed SLMA significantly broadens the angular performance of the MA up to near grazing angles (about 80°), where high absorptivity is still achieved in both principal planes. The deteriorating effect of diffraction modes has been comprehensively analyzed. In comparison to the previous wide-angle MA reports based on intricate particle geometries and brute-force optimizations, the proposed design features a straightforward semi-analytical algorithm, which can also be re-developed for microwave, mid-infrared, and optical frequency bands and for any type of MA element. The proposed SLMA would be very promising for various wavelength-selective applications such as sensors and imaging.
Increased both PD–L1 and PD–L2 expressions on monocytes of patients with hepatocellular carcinoma was associated with a poor prognosis
Authors: Yasuoka Hidetaka , Asai Akira , Ohama Hideko , Tsuchimoto Yusuke , Fukunishi Shinya , Higuchi Kazuhide 
Published: June 2020

AbstractAnti-programmed cell death-1 (PD-1) antibodies has been approved to treat HCC. Some PD-1 ligands (PD–L1 and PD–L2) negative tumors respond to treatment of anti-PD-1 antibodies, and this fact may be caused by the expression of PD-1 ligands on non-tumor cells. PD–L1 was recently found to be expressed on CD14+ cells from cancer patients. We investigate PD-1 ligands expression on CD14+ cells of patients with HCC and the role of CD14+ cells in an antitumor response. In this study, 87 patients diagnosed with HCC were enrolled. CD14+ cells from patients with HCC expressed PD–L1 (4.5–95.5%) and PD–L2 (0.2–95.0%). According to cut-off values, we classified patients as those either with PD–L1+PD–L2+CD14+ cells or other types of CD14+ cells. The overall survival of patients with PD–L1+PD–L2+CD14+ cells was shorter than that of patients with other types of CD14+ cells (p = 0.0023). PD–L1+PD–L2+CD14+ cells produced IL-10 and CCL1, and showed little tumoricidal activity against HepG2 cells. The tumoricidal activity of CD8+ cells from patients with PD–L1+PD–L2+CD14+ cells were suppressed by co-cultivation with CD14+ cells from the syngeneic patient. Furthermore, anti-PD-1 antibody restored their tumoricidal activity of CD8+ cells. In conclusion, some patients with HCC have PD–L1+PD–L2+CD14+ cells that suppress their antitumor response. These inhibitory functions of CD14+ cells may be associated with a poor prognosis in these patients.
The relationship between neutrophil–lymphocyte ratio and in-stent restenosis in superficial femoral artery
Authors: Yang Yaobo , Ge Fangfang , Shen Jing , Song Jianbo , Xie Jiapei , Qu Jiangshuai , Mao Xinzu , Kuang Zhaocheng , Wang Xiang , Wu Yejun , Wang Shenghai , Xiao Liang 
Published: June 2020

Abstract
The present study aimed to investigate the relationship between an increase in the pre- and post-operative neutrophil–lymphocyte ratio (NLR) and superficial femoral artery in-stent restenosis (ISR) rate. We recruited 199 patients that underwent superficial femoral artery stenting for lower extremity arteriosclerosis obliterans at our hospital from March 2015 to July 2018. Patients were divided into two groups according to the occurrence of ISR within 1 year (group 1, ISR and group 2, Non-ISR). The after NLR (NLRafter) and NLR change ratio (NLRratio) (P&lt;0.001) were significantly higher in group 1. A NLRafter &gt; 4.3 was associated with an odds ratio of 1.946 (95% CI [1.51–2.50]; P&lt;0.001) for the presence of ISR. A NLRratio &gt; 37.5% was associated with an odds ratio of 3.6 (95% CI [2.03–6.36]; P&lt;0.001) for occurrence of ISR. A NLRafter level &gt; 4.3 had 75% sensitivity and 76% specificity for the prediction of ISR, as identified by the ROC curve. A NLRratio level &gt; 37.5% predicted ISR with 77% sensitivity and 60% specificity. Multivariate logistic regression analysis demonstrated that NLRratio was the strongest independent predictor of ISR (P&lt;0.001). In conclusions, NLRratio could be used as a prognostic marker in superficial femoral artery stents.
Partner-Specific Communication Deficits in Individuals With Alzheimer's Disease
Authors: Paek Eun Jin , Yoon Si On 
Published: June 2020

PurposeSpeakers adjust referential expressions to the listeners' knowledge while communicating, a phenomenon called “audience design.” While individuals with Alzheimer's disease (AD) show difficulties in discourse production, it is unclear whether they exhibit preserved partner-specific audience design. The current study examined if individuals with AD demonstrate partner-specific audience design skills.MethodTen adults with mild-to-moderate AD and 12 healthy older adults performed a referential communication task with two experimenters (E1 and E2). At first, E1 and participants completed an image-sorting task, allowing them to establish shared labels. Then, during testing, both experimenters were present in the room, and participants described images to either E1 or E2 (randomly alternating). Analyses focused on the number of words participants used to describe each image and whether they reused shared labels.ResultsDuring testing, participants in both groups produced shorter descriptions when describing familiar images versus new images, demonstrating their ability to learn novel knowledge. When they described familiar images, healthy older adults modified their expressions depending on the current partner's knowledge, producing shorter expressions and more established labels for the knowledgeable partner (E1) versus the naïve partner (E2), but individuals with AD were less likely to do so.ConclusionsThe current study revealed that both individuals with AD and the control participants were able to acquire novel knowledge, but individuals with AD tended not to flexibly adjust expressions depending on the partner's knowledge state. Conversational inefficiency and difficulties observed in AD may, in part, stem from disrupted audience design skills.
The Efficacy of Collaborative Referencing Intervention in Chronic Aphasia: A Mixed-Methods Study
Authors: Devanga Suma R. , Sherrill Martha , Hengst Julie A. 
Published: June 2020

Purpose
The feasibility of a collaborative referencing intervention (CRI) for adults with chronic aphasia has been documented in two descriptive case studies (Devanga, 2014; Hengst et al., 2010, 2008). The current Phase II mixed-methods treatment study replicates the CRI with four additional participants (using interpretive research) and investigates how it impacts a traditional measure, participants' confrontational naming abilities, outside of game play (using multiple-probe single-case experimental design).

Method
Four adults with chronic aphasia participated in the study composed of (a) three preparatory sessions, (b) five baseline sessions, (c) 15 CRI sessions with five treatment probes, and (d) six maintenance sessions. A collaborative confrontation naming (CCN) probe (i.e., dependent variable) was administered in each baseline, treatment probe, and maintenance session. Each CRI session (i.e., independent variable) consisted of a photo-matching game with participant and clinician partner taking alternative turns identifying and matching personally relevant treatment cards. CCN probes were scored using a multidimensional rating scale. Fidelity and social validity were also assessed.

Results
Replication of the CRI showed successful and consistent referential learning in all four participant pairs. The multiple-probe analysis of CCN revealed a positive treatment effect on naming in three participants indicating that the CRI was efficacious. High fidelity was maintained throughout the study. Social validity interviews revealed positive outcomes and significant impacts of treatment on the participants' lives.

Conclusion
The CRI demonstrates strong clinical implications for adults with chronic aphasia. Future research exploring the treatment effectiveness and the implementation to a variety of clinical settings is warranted.
Meaningful Transitions: Enhancing Clinician Roles in Transition Planning for Adolescents With Autism Spectrum Disorders
Authors: Perryman Twyla , Ricks Lacey , Cash-Baskett Labrita 
Published: June 2020

PurposeThe purpose of this tutorial is to provide speech-language pathologists (SLPs) with foundational information that will assist them in transition planning for students with autism spectrum disorder (ASD) based on a review of current literature. SLPs must be knowledgeable of transition planning in order to assist students with ASD and their families with preparing for their future. An appreciation and awareness of pertinent assessments, functional goals, and factors associated with successful postsecondary outcomes are essential competencies that SLPs need when planning for the transition process. SLPs are ideal workforce development partners. They facilitate independence, communication, and interaction skills necessary for postsecondary and workplace success. Speech-language services are one of the most common special education services received by high school students with Individualized Education Programs. However, SLPs receive little preparation on the specifics or nuances of transition planning prior to working in the educational settings, despite the high incidence of speech-language services in secondary education.MethodThis tutorial reviews and synthesizes research findings related to assessment planning, goal-setting, and Individualized Education Program implementation for achieving meaningful postsecondary transitions for students with ASD. Additionally, it highlights some of the key postsecondary skillsets related to speech-language therapy services, including the development of self-determination, self-advocacy, social competence, and adaptive behaviors.ConclusionGreater focus on higher quality transition planning requires SLPs to develop high levels of knowledge and competencies in the transition planning process. This tutorial educates clinicians on the unique challenges faced by individuals with ASD and provides evidence-based strategies to help students and families successfully plan for and navigate postsecondary transitions.
Applying saliency-map analysis in searches for pulsars and fast radio bursts
Authors: Zhang C. , Wang C. , Hobbs G. , Russell C. J. , Li D. , Zhang S.-B. , Dai S. , Wu J.-W. , Pan Z.-C. , Zhu W.-W. , Toomey L. , Ren Z.-Y. 
Published: June 2020

Context. We investigate the use of saliency-map analysis to aid in searches for transient signals, such as fast radio bursts and individual pulses from radio pulsars.
Aims. Our aim is to demonstrate that saliency maps provide the means to understand predictions from machine learning algorithms and can be implemented in pipelines used to search for transient events.
Methods. We implemented a new deep learning methodology to predict whether any segment of the data contains a transient event. The algorithm was trained using real and simulated data sets. We demonstrate that the algorithm is able to identify such events. The output results are visually analysed via the use of saliency maps.
Results. We find that saliency maps can produce an enhanced image of any transient feature without the need for de-dispersion or removal of radio frequency interference. The maps can be used to understand which features in the image were used in making the machine learning decision and to visualise the transient event. Even though the algorithm reported here was developed to demonstrate saliency-map analysis, we have detected a single burst event, in archival data, with dispersion measure of 41 cm−3 pc that is not associated with any currently known pulsar.
Das Nagoya-Protokoll
Authors: Stern Dennis 
Published: June 2020

ZusammenfassungDas Nagoya-Protokoll ist ein bindender, transnationaler Vertrag, der unter der Berücksichtigung des Schutzes der Biodiversität einen gerechten Vorteilsausgleich für die Nutzung genetischer Ressourcen, wie z. B. Pflanzen zur Arzneimittel-herstellung sicherstellen soll. Aufgrund der enormen Vielfalt nehmen Pflanzen eine signifikante Rolle für die Erforschung neuer pharmazeutischer Wirkstoffe ein. Vor diesem Hintergrund sowie der Vielschichtigkeit des Nagoya-Protokolls ist die nähere Betrachtung der rechtlichen Vorgaben sowohl für Hersteller als auch für nicht-kommerzielle Forschungseinrichtungen von großer Bedeutung.