bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence, type distribution and risk factors for oral HPV in Danish renal transplant recipients
Authors: Faber Mette T. , Kjær Alexander K. , Larsen Helle K. , Thomsen Louise T. , Hædersdal Merete , Bonde Jesper , Hansen Jesper M. , Sørensen Søren S. , Kjær Susanne K. 
Published: November 2019

AbstractObjectiveTo assess the prevalence and type distribution of oral human papillomavirus (HPV) among renal transplant recipients (RTRs) and healthy controls and to examine risk factors for oral HPV among RTRs.Materials and MethodsDuring 2016‐2017 we recruited 250 RTRs and 250 controls. Oral samples were tested for HPV DNA with INNO‐LiPA HPV Genotyping Extra II. All participants answered a questionnaire on lifestyle and sexual behaviour, and characteristics of RTRs were obtained from medical files. We assessed prevalence and type distribution of oral HPV. Using logistic regression, the risk of oral HPV and risk factors for oral HPV among RTRs were estimated as odds ratios (OR) with 95% confidence intervals (CI).ResultsOverall, 30 RTRs (12.1%) and 26 controls (10.4%) were oral HPV positive (OR = 1.14; 95% CI: 0.64–2.05). Female RTRs tended to have a higher oral HPV prevalence than controls (OR = 1.73; 95% CI: 0.63–4.77), while no difference was observed among men. HPV51 was the commonest genotype. Sexual behaviour tended to be associated with oral HPV among RTRs.ConclusionsThere was no overall difference in oral HPV prevalence between RTRs and controls, but female RTRs tended to have a higher prevalence of oral HPV than controls.
Can the power of platforms be harnessed for governance?
Authors: Ansell Christopher , Miura Satoshi 
Published: November 2019

AbstractAlthough not as eye‐catching as their business counterparts, many public and private institutions are currently experimenting with using platforms as a strategy of governance. Governance platforms are now being constructed by a wide array of actors at different geographical scales and across a wide range of issue areas. Although often enabled by digital technology, governance platforms fundamentally embody a new organizing logic to achieve distributed participation and mobilization. While private platforms are transforming the way that companies create and market their products or services and shifting the fundamental logic of how value is produced and appropriated, can this powerful organizing logic be harnessed for public as well as private purposes? We investigate how governance platforms generate powerful effects and survey the extant literature on governance platforms. We conclude that governance platforms do demonstrate promise, although they face a number of challenges.
Genome‐wide association study identifies an NLR gene that confers partial resistance to Magnaporthe oryzae in rice
Authors: Liu Ming‐Hao , Kang Houxiang , Xu Yucheng , Peng Ye , Wang Dan , Gao Lijun , Wang Xuli , Ning Yuese , Wu Jun , Liu Wende , Li Chengyun , Liu Bin , Wang Guo‐Liang 
Published: November 2019

SummaryBecause of the frequent breakdown of major resistance (R) genes, identification of new partial R genes against rice blast disease is an important goal of rice breeding. In this study, we used a core collection of the Rice Diversity Panel II (C‐RDP‐II), which contains 584 rice accessions and are genotyped with 700 000 single‐nucleotide polymorphism (SNP) markers. The C‐RDP‐II accessions were inoculated with three blast strains collected from different rice‐growing regions in China. Genome‐wide association study identified 27 loci associated with rice blast resistance (LABRs). Among them, 22 LABRs were not associated with any known blast R genes or QTLs. Interestingly, a nucleotide‐binding site leucine‐rich repeat (NLR) gene cluster exists in the LABR12 region on chromosome 4. One of the NLR genes is highly conserved in multiple partially resistant rice cultivars, and its expression is significantly up‐regulated at the early stages of rice blast infection. Knockout of this gene via CRISPR‐Cas9 in transgenic plants partially reduced blast resistance to four blast strains. The identification of this new non‐strain specific partial R gene, tentatively named rice blast Partial Resistance gene 1 (PiPR1), provides genetic material that will be useful for understanding the partial resistance mechanism and for breeding durably resistant cultivars against blast disease of rice.
Work, welfare, and wellbeing: The impacts of welfare conditionality on people with mental health impairments in the UK
Authors: Dwyer Peter , Scullion Lisa , Jones Katy , McNeill Jenny , Stewart Alasdair B. R. 
Published: November 2019

AbstractThe personal, economic, and social costs of mental ill health are increasingly acknowledged by many governments and international organisations. Simultaneously, in high‐income nations, the reach of welfare conditionality has extended to encompass many people with mental health impairments as part of on‐going welfare reforms. This is particularly the case in the UK where, especially since the introduction of Employment and Support Allowance in 2008, the rights and responsibilities of disabled people have been subject to contestation and redefinition. Following a review of the emergent international evidence on mental health and welfare conditionality, this paper explores two specific issues. First, the impacts of the application of welfare conditionality on benefit claimants with mental health impairments. Second, the effectiveness of welfare conditionality in supporting people with experience of mental ill health into paid work. In considering these questions, this paper presents original analysis of data generated in qualitative longitudinal interviews with 207 UK social security benefit recipients with experience of a range of mental health issues. The evidence suggests that welfare conditionality is largely ineffective in moving people with mental health impairments into, or closer to, paid work. Indeed, in many cases, it triggers negative health outcomes that make future employment less likely. It is concluded that the application of conditionality for people with mental health issues is inappropriate and should cease.
Operation of the boreal peatland methane cycle across the past 16 k.y.
Authors: Zheng Yanhong , Fang Zhengkun , Fan Tongyu , Liu Zhao , Wang Zhangzhang , Li Qiyuan , Pancost Richard D. , Naafs B. David A. 
Published: November 2019

Abstract
The role of boreal wetlands in driving variations in atmospheric methane (CH4) concentrations across the last deglaciation (20–10 ka) and the Holocene is debated. Most studies infer the sources of atmospheric methane via ice-core records of methane concentration and its light stable isotopic composition. However, direct evidence for variations in the methane cycle from the wetlands themselves is relatively limited. Here, we used a suite of biomarker proxies to reconstruct the methane cycle in the Chinese Hani peat across the past 16 k.y. We found two periods of enhanced methanogenesis, at ca. 15–11 ka and ca. 10–6 ka, whereas weak methanogenesis characterized the late Holocene. These periods of enhanced methanogenesis relate to periods of high/increasing temperatures, supporting a temperature control on the wetland methane cycle. We found no biomarker evidence for intense methanotrophy throughout the past 16 k.y., and, contrary to previous studies, we found no clear control of hydrology on the peatland methane cycle. Although the onset of methanogenesis at Hani at ca. 15 ka coincided with a negative shift in methane δ13C in the ice cores, there is no consistent correlation between changes in the reconstructed methane cycle of the boreal Hani peat and atmospheric CH4 concentrations.
Triple Higgs boson production to six b-jets at a 100 TeV proton collider
Authors: Papaefstathiou Andreas , Tetlalmatzi-Xolocotzi Gilberto , Zaro Marco 
Published: November 2019

AbstractWe investigate the production of three Higgs bosons at a proton-proton collider running at a centre-of-mass energy of 100 TeV, all of which decay into b-jets. This final state encapsulates by far the largest fraction of the total cross section of triple Higgs boson production, approximately $$20\%$$20%. We examine, by constructing detailed phenomenological analyses, two scenarios: (i) one in which the triple and quartic Higgs boson self-couplings are modified independently by new phenomena with respect to their Standard Model (SM) values and (ii) an extension of the SM by a gauge-singlet scalar that could drive first-order electroweak phase transition, within the context of the so-called xSM. In the former, we find that competitive constraints of $${\mathscr {O}}(1)$$O(1) can be placed on the quartic coupling and in the latter we demonstrate that it will be possible to obtain important information on the structure of the extended scalar sector.
Up-down asymmetries of charmed baryon three-body decays
Authors: Cen Jian-Yong , Geng Chao-Qiang , Liu Chia-Wei , Tsai Tien-Hsueh 
Published: November 2019

AbstractWe study the up-down asymmetries in the three-body anti-triplet charmed baryon decays of $$\mathbf{B}_{\mathbf{c}}\rightarrow \mathbf{B}_{\mathbf{n}}MM' $$Bc→BnMM′ with the $$SU(3)_f$$SU(3)f flavor symmetry, where $$\mathbf{B}_{\mathbf{c}}$$Bc presents the anti-triplet charmed baryon of $$(\Xi _c^0,-\Xi _c^+,\Lambda _c^+)$$(Ξc0,-Ξc+,Λc+), while $$\mathbf{B}_{\mathbf{n}}$$Bn and $$M^{(')}$$M(′) denote octet baryon and meson states, respectively. By assuming the s-wave meson-pairs to be the dominant constituents in final state configurations, we can write the spin-dependent decay amplitude into parity-conserving and parity-violating parts, parametrized by 6 real parameters under $$SU(3)_f$$SU(3)f, respectively. Fitting these parameters by 16 experimental data points with the minimum $$\chi ^2$$χ2 method, we obtain that $$\chi ^2/d.o.f=2.4$$χ2/d.o.f=2.4. With the fitted parameters, we evaluate the up-down asymmetries along with the decay branching ratios of $$\mathbf{B}_{\mathbf{c}}\rightarrow \mathbf{B}_{\mathbf{n}}MM' $$Bc→BnMM′. Some of these up-down asymmetries are accessible to the experiments at BESIII, BELLE-II and LHCb.
An Engineered Tumor-on-a-Chip Device with Breast Cancer–Immune Cell Interactions for Assessing T-cell Recruitment
Authors: Aung Aereas , Kumar Vardhman , Theprungsirikul Jomkuan , Davey Shruti K. , Varghese Shyni 
Published: November 2019

AbstractRecruitment of immune cells to a tumor is determined by the complex interplay between cellular and noncellular components of the tumor microenvironment. Ex vivo platforms that enable identification of key components that promote immune cell recruitment to the tumor could advance the field significantly. Herein, we describe the development of a perfusable multicellular tumor-on-a-chip platform involving different cell populations. Cancer cells, monocytes, and endothelial cells were spatially confined within a gelatin hydrogel in a controlled manner by using 3D photopatterning. The migration of the encapsulated endothelial cells against a chemokine gradient created an endothelial layer around the constructs. Using this platform, we examined the effect of cancer cell–monocyte interaction on T-cell recruitment, where T cells were dispersed within the perfused media and allowed to infiltrate. The hypoxic environment in the spheroid cultures recruited more T cells compared with dispersed cancer cells. Moreover, the addition of monocytes to the cancer cells improved T-cell recruitment. The differences in T-cell recruitment were associated with differences in chemokine secretion including chemokines influencing the permeability of the endothelial barrier. This proof-of-concept study shows how integration of microfabrication, microfluidics, and 3D cell culture systems could be used for the development of tumor-on-a-chip platforms involving heterotypic cells and their application in studying recruitment of cells by the tumor-associated microenvironment.Significance:This study describes how tumor-on-chip platforms could be designed to create a heterogeneous mix of cells and noncellular components to study the effect of the tumor microenvironment on immune cell recruitment.
Targeting PD-L1 Initiates Effective Antitumor Immunity in a Murine Model of Cushing Disease
Authors: Kemeny Hanna R. , Elsamadicy Aladine A. , Farber S. Harrison , Champion Cosette D. , Lorrey Selena J. , Chongsathidkiet Pakawat , Woroniecka Karolina I. , Cui Xiuyu , Shen Steven H. , Rhodin Kristen E. , Tsvankin Vadim , Everitt Jeffrey , Sanchez-Perez Luis , Healy Patrick , McLendon Roger E. , Codd Patrick J. , Dunn Ian F. , Fecci Peter E. 
Published: November 2019

Abstract

Purpose:
Although pituitary adenoma is classified as benign, Cushing disease is associated with significant morbidity due to the numerous sequelae of elevated cortisol levels. Successful therapy for Cushing disease remains elusive due to high rates of treatment-refractory recurrence. The frequent emergence of lymphocytic hypophysitis following checkpoint blockade for other cancers, as well as the expression of PD-L1 on pituitary adenomas, suggest a role for immunotherapy.

Experimental Design:
This study confirms PD-L1 expression on functioning pituitary adenomas and is the first to evaluate the efficacy of checkpoint blockade (anti–PD-L1) therapy in a preclinical model of Cushing disease.

Results:
Herein, treatment with anti–PD-L1 was successful in reducing adrenocorticotropic hormone plasma levels, decreasing tumor growth, and increasing survival in our model. Furthermore, tumor-infiltrating T cells demonstrated a pattern of checkpoint expression similar to other checkpoint blockade–susceptible tumors.

Conclusions:
This suggests that immunotherapy, particularly blockade of the PD1/PD-L1 axis, may be a novel therapeutic option for refractory Cushing disease. Clinical investigation is encouraged.
The Existence of MTH1-independent 8-oxodGTPase Activity in Cancer Cells as a Compensatory Mechanism against On-target Effects of MTH1 Inhibitors
Authors: Samaranayake Govindi J. , Troccoli Clara I. , Zhang Ling , Huynh Mai , Jayaraj Christina J. , Ji Debin , McPherson Lisa , Onishi Yoshiyuki , Nguyen Dao M. , Robbins David J. , Karbaschi Mahsa , Cooke Marcus S. , Barrientos Antonio , Kool Eric T. , Rai Priyamvada 
Published: November 2019

Abstract
Investigations into the human 8-oxodGTPase, MutT Homolog 1 (MTH1), have risen sharply since the first-in-class MTH1 inhibitors were reported to be highly tumoricidal. However, MTH1 as a cancer therapeutic target is currently controversial because subsequently developed inhibitors did not exhibit similar cytotoxic effects. Here, we provide the first direct evidence for MTH1-independent 8-oxodGTPase function in human cancer cells and human tumors, using a novel ATP-releasing guanine-oxidized (ARGO) chemical probe. Our studies show that this functionally redundant 8-oxodGTPase activity is not decreased by five different published MTH1-targeting small molecules or by MTH1 depletion. Significantly, while only the two first-in-class inhibitors, TH588 and TH287, reduced cancer cell viability, all five inhibitors evaluated in our studies decreased 8-oxodGTPase activity to a similar extent. Thus, the reported efficacy of the first-in-class MTH1 inhibitors does not arise from their inhibition of MTH1-specific 8-oxodGTPase activity. Comparison of DNA strand breaks, genomic 8-oxoguanine incorporation, or alterations in cellular oxidative state by TH287 versus the noncytotoxic inhibitor, IACS-4759, contradict that the cytotoxicity of the former results solely from increased levels of oxidatively damaged genomic DNA. Thus, our findings indicate that mechanisms unrelated to oxidative stress or DNA damage likely underlie the reported efficacy of the first-in-class inhibitors. Our study suggests that MTH1 functional redundancy, existing to different extents in all cancer lines and human tumors evaluated in our study, is a thus far undefined factor which is likely to be critical in understanding the importance of MTH1 and its clinical targeting in cancer.
Rational Combination Therapy for Melanoma with Dinaciclib by Targeting BAK-Dependent Cell Death
Authors: Xu Xiaoou , Eshima Shizuka , Kato Shinichiro , Fisher David E. , Sakurai Hiroaki , Hayakawa Yoshihiro , Yokoyama Satoru 
Published: November 2019

Abstract
Mutation of the oncogene BRAF is among the most common genetic alterations in melanoma. BRAF inhibitors alone or in combination with MEK inhibitors fail to eradicate the tumor in most patients due to combinations of intrinsic or acquired resistance. Therefore, novel strategies are needed to improve the therapeutic efficacy of BRAF inhibition. We demonstrated that dinaciclib has potent antimelanoma effects by inducing BAK-dependent apoptosis through MCL1 reduction. Contrary to dinaciclib, the inhibitors of BRAF/MEK/CDK4/6 induced apoptosis dominantly through a BAX-dependent mechanism. Although the combination of BRAF and MEK inhibitors did not exhibit additive antimelanoma effects, their combination with dinaciclib synergistically inhibited melanoma growth both in vitro and in vivo. Collectively, our present findings suggest dinaciclib to be an effective complementary drug of BAX-dependent antimelanoma drugs by targeting BAK-mediated apoptosis, and other such rational drug combinations can be determined by identifying complementary drugs activating either BAK or BAX.
HSF1-Mediated Control of Cellular Energy Metabolism and mTORC1 Activation Drive Acute T-Cell Lymphoblastic Leukemia Progression
Authors: Eroglu Binnur , Pang Junfeng , Jin Xiongjie , Xi Caixia , Moskophidis Demetrius , Mivechi Nahid F. 
Published: November 2019

Abstract

Deregulated oncogenic signaling linked to PI3K/AKT and mTORC1 pathway activation is a hallmark of human T-cell acute leukemia (T-ALL) pathogenesis and contributes to leukemic cell resistance and adverse prognosis. Notably, although the multiagent chemotherapy of leukemia leads to a high rate of complete remission, options for salvage therapy for relapsed/refractory disease are limited due to the serious side effects of augmenting cytotoxic chemotherapy. We report that ablation of HSF1, a key transcriptional regulator of the chaperone response and cellular bioenergetics, from mouse T-ALL tumors driven by PTEN loss or human T-ALL cell lines, has significant therapeutic effects in reducing tumor burden and sensitizing malignant cell death. From a mechanistic perspective, the enhanced sensitivity of T-ALLs to HSF1 depletion resides in the reduced MAPK–ERK signaling and metabolic and ATP-producing capacity of malignant cells lacking HSF1 activity. Impaired mitochondrial ATP production and decreased intracellular amino acid content in HSF1-deficient T-ALL cells trigger an energy-saving adaptive response featured by attenuation of the mTORC1 activity, which is coregulated by ATP, and its downstream target proteins (p70S6K and 4E-BP). This leads to protein translation attenuation that diminishes oncogenic signals and malignant cell growth. Collectively, these metabolic alterations in the absence of HSF1 activity reveal cancer cell liabilities and have a profound negative impact on T-ALL progression.

Implications:
Targeting HSF1 and HSF1-dependent cancer-specific anabolic and protein homeostasis programs has a significant therapeutic potential for T-ALL and may prevent progression of relapsed/refractory disease.
Refined Sphenopalatine Ganglion Stimulator Placement and Intensity Setting to Augment Blood Flow and Neurologic Function
Authors: Saver Jeffrey L. , Kharaishvili Nino , Janelidze Tamar , Beridze Maia , Zarqua Natia , Solberg Yoram , Bornstein Natan M. ,   for the IMPACT-24M Trial Investigators, Khachidze Natia , Avazashvili Ivane , Meshviliani Paata , Mamardashvili Ekaterine , Beridze Nino , Avazashvili Ivane , Gulua Tamaz , Phiphia Giorgi 
Published: November 2019

Background and Purpose—
Two large, randomized trials indicated that sphenopalatine ganglion (SPG) stimulation improves final disability outcome in acute anterior circulation patients with ischemic stroke with confirmed cortical involvement. This study evaluated 2 refinements in SPG stimulation treatment technique: (1) SPG electrode placement with real-time optical tracking guidance; and (2) stimulation intensity comfortable tolerance level selection using non-noxious facial physiological markers.

Methods—
This study was a single, active arm trial at 4 centers, enrolling patients with anterior circulation ischemic stroke, National Institutes of Health Stroke Scale 1 to 6 including arm weakness subitem score ≥1, not receiving recanalization therapies, and within 24 hours of onset. Stimulation level was set based on ipsilateral facial tingling sensation or lacrimation. SPG stimulation effects were assessed by measuring volumetric blood flow in the ipsilateral common carotid artery by ultrasound and grasp and pinch strength in the affected hand before and during stimulation, and by change in National Institutes of Health Stroke Scale from day 1 to 7.

Results—

Among 50 enrolled patients, age was median 66 years (interquartile range, 60–74), 44% were female, National Institutes of Health Stroke Scale median was 5 (interquartile range, 4–5), and median onset-to-screening time was 18 hours (interquartile range, 9–20). Median implantation skin-to-skin time was 4 minutes (interquartile range, 3–7), and all 50 implants were placed correctly. Comfortable tolerance level was found based on physiological biomarkers in 96% of patients, including 86% in the optimal, low-medium intensity range. SPG stimulation significantly increased common carotid artery peak systolic and end-diastolic blood flow (44%,
P
<0.0001; and 52%,
P
<0.0001) and improved pinch strength (42%,
P
<0.0001) and grasp strength (26%,
P
<0.0001). Degree of National Institutes of Health Stroke Scale recovery by day 7 was greater than in matched historic controls, median 75% versus 50%,
P
=0.0003.

Conclusions—
SPG stimulator placement with real-time optical tracking guidance was fast and accurate, and selection of stimulation intensity levels based on non-noxious facial tingling and lacrimation was feasible in nearly all patients. SPG stimulation led to cervico-cranial blood flow augmentation and improved hand motor function.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03551093.
Overseas Chinese Educational Strategies and Its Policy Implications
Authors: Zheng (郑丽洁) Lijie , de Haan Mariëtte , Koops Willem 
Published: November 2019

Abstract
This paper assesses whether China’s policies for providing educational support to overseas Chinese match the educational needs of current Chinese immigrants around the world. Firstly, the paper presents the different migration backgrounds of four waves of Chinese global migration in contemporary history: labor immigrants to the Global North, international students in the Global North, businessmen in the Global South and the new rich investors in the Global North. Using the concept of intergenerational contract, we found the four waves have distinct parental investment strategies in relation to their migration background, which comes along with their different educational needs. After carefully reviewing China’s policies in overseas education in terms of the assumptions, purpose and background of their implementation, we argue that these policies are outdated and serve the needs of only a limited number of Chinese immigrants due to their ignoring the variety of certain intergenerational contracts. Lastly, some specific suggestions for policy makers are given.