bluuebunny/crossref_metadata_2025_split huggingface dataset:
A non-randomized pilot study to test the feasibility of treating chronic pain and opioid prescription use in rural areas with acceptance and commitment therapy (T-PACT)
Authors: Rhyne Robert L , Rishel Brakey Heidi , Halladay Jacquie R. , Mottus Kathleen , Greiner K. Allen , Salt Elizabeth , Myers Orrin , Sutton Kent , Fuentes Jesus , Vowles Kevin E. 
Published: March 2020

AbstractChronic non-cancer pain (CNCP) involves one-third of the US population, and prescription opioids contribute to the opioid epidemic. The Centers for Disease Control and Prevention emphasizes maximizing non-opioid treatment, but many rural populations cannot access alternative therapies. Clinical and Translational Science Award hubs across four rural states performed a multi-site, single-arm intervention feasibility study testing methods and procedures of implementing a behavioral intervention, acceptance and commitment therapy, in primary care CNCP patients on chronic opioids. Using the CONSORT extension for feasibility studies, we describe lessons learned in recruiting/retaining participants, intervention implementation, data measurement, and multi-site procedures. Results inform a future definitive trial and potentially others conducting rural trials.
Toward the Golden Bull and against the Pope: The Role of Custom and Honor in King Ludwig IV's Nuremberg and Frankfurt Appellations (1323–24)
Authors: Lord Kevin Lucas 
Published: March 2020

AbstractThis article addresses the onset of a decades-long conflict between the ruler of the Holy Roman Empire King Ludwig IV of Bavaria and the papacy. When Ludwig intervened on behalf of antipapal factions in northern Italy in 1323, Pope John XXII issued an ultimatum demanding that Ludwig immediately cease to exercise the royal power and title on the pretext that he had never received papal approval of his royal election. Failure to comply meant that the king would fall under sentence of excommunication. Ludwig responded with nearly identical appeals issued in Nuremberg and Frankfurt. Against previous arguments that these appeals were either legal documents operating within the confines of Roman Canon law or artifacts of protomodern realpolitik, this article argues that the “Nuremberg” and “Frankfurt Appellations” emerged from the king's preoccupation with his honor. His Appellations utilized the language and form of Roman Canon law to defame his opponent while he sought to ennoble and justify his actions with a rhetoric mirroring that in supposed repositories of imperial customary law such as theSachsen- andSchwabenspiegel. In arguing that German custom superseded the jurisdiction of papal law in his Appellations, Ludwig elevated a discourse concerning royal elections to the highest levels of imperial politics where it would remain and find inclusion, in intent if not precise formulation, in the famed Golden Bull of 1356.
The effect of dual inhibition of Ras–MEK–ERK and GSK3β pathways on development ofin vitrocultured rabbit embryos
Authors: Bontovics Babett , Maraghechi Pouneh , Lázár Bence , Anand Mahek , Németh Kinga , Fábián Renáta , Vašíček Jaromír , Makarevich Alexander V. , Gócza Elen , Chrenek Peter 
Published: March 2020

SummaryDual inhibition (2i) of Ras–MEK–ERK and GSK3β pathways enables the derivation of embryo stem cells (ESCs) from refractory mouse strains and, for permissive strains, allows ESC derivation with no external protein factor stimuli involvement. In addition, blocking of ERK signalling in 8-cell-stage mouse embryos leads to ablation of GATA4/6 expression in hypoblasts, suggesting fibroblast growth factor (FGF) dependence of hypoblast formation in the mouse. In human, bovine or porcine embryos, the hypoblast remains unaffected or displays slight-to-moderate reduction in cell number. In this study, we demonstrated that segregation of the hypoblast and the epiblast in rabbit embryos is FGF independent and 2i treatment elicits only a limited reinforcement in favour of OCT4-positive epiblast populations against the GATA4-/6-positive hypoblast population. It has been previously shown that TGFβ/Activin A inhibition overcomes the pervasive differentiation and inhomogeneity of rat iPSCs, rat ESCs and human iPSCs while prompting them to acquire naïve properties. However, TGFβ/Activin A inhibition, alone or together with Rho-associated, coiled-coil containing protein kinase (ROCK) inhibition, was not compatible with the viability of rabbit embryos according to the ultrastructural analysis of preimplantation rabbit embryos by electron microscopy. In rabbit models ovulation upon mating allows the precise timing of progression of the pregnancy. It produces several embryos of the desired stage in one pregnancy and a relatively short gestation period, making the rabbit embryo a suitable model to discover the cellular functions and mechanisms of maintenance of pluripotency in embryonic cells and the embryo-derived stem cells of other mammals.
RELATIVE UNITARY RZ-SPACES AND THE ARITHMETIC FUNDAMENTAL LEMMA
Authors: Mihatsch Andreas 
Published: March 2020

AbstractWe prove a comparison isomorphism between certain moduli spaces of$p$-divisible groups and strict${\mathcal{O}}_{K}$-modules (RZ-spaces). Both moduli problems are of PEL-type (polarization, endomorphism, level structure) and the difficulty lies in relating polarized$p$-divisible groups and polarized strict${\mathcal{O}}_{K}$-modules. We use the theory of relative displays and frames, as developed by Ahsendorf, Lau and Zink, to translate this into a problem in linear algebra. As an application of these results, we verify new cases of the arithmetic fundamental lemma (AFL) of Wei Zhang: The comparison isomorphism yields an explicit description of certain cycles that play a role in the AFL. This allows, under certain conditions, to reduce the AFL identity in question to an AFL identity in lower dimension.
The Origins and Evolution of Vietnam'sDoi MoiForeign Policy of 1986
Authors: Path Kosal 
Published: March 2020

AbstractDrawing on new archival evidence, this paper focuses on the origins of Vietnam's foreign economic policy of 1986, better known asdoi moi(renovation). The existing scholarship contends thatdoi moiideas emerged amid Vietnam's socio-economic crisis during the late 1970s through a bottom-up process of market-oriented activities by local authorities. I argue, however, that these scholars overlooked the early ideas of economically engaging the West to obtain advanced technology to raise the Vietnamese products’ quality, and therefore, their competitiveness in the socialist bloc. Following the Paris Peace Accords in January 1973, Vietnamese diplomats-turned reformists studied the role of western technology and capital investment in the Soviet Union and Eastern Europe. The Politburo entrusted Vice-Minister of Foreign Affairs Nguyen Co Thach, a senior advisor to Hanoi's chief negotiator Le Duc Tho in Paris, to conduct a series of clandestine studies on the role of western technology in economic relations between East and West. Thach's learning about the West's technological revolution led them to the shocking conclusion that the Soviet bloc was at least a decade behind the West in technological development. The fear of Vietnam being trapped in economic backwardness propelled these reformers to advocate bold ideas of economically engaging the West in the post-Vietnam War era to extract advanced technology to support post-war economic development and modernisation. However, it took an economic crisis (1977–78), followed by another costly two-front war against Cambodia and China between 1979 and 1985, for reformist Nguyen Co Thach's ideas to prevail over the conservative faction's military-first policy.
Scaling Point‐Scale (Pedo)transfer Functions to Seamless Large‐Domain Parameter Estimates for High‐Resolution Distributed Hydrologic Modeling: An Example for the Rhine River
Authors: Imhoff R. O. , van Verseveld W. J. , van Osnabrugge B. , Weerts A. H. 
Published: March 2020

AbstractMoving toward high‐resolution gridded hydrologic models asks for novel parametrization approaches. A high‐resolution conceptual hydrologic model (wflow_sbm) was parameterized for the Rhine basin in Europe based on point‐scale (pedo)transfer functions, without further calibration of effective model parameters on discharge. Parameters were estimated on the data resolution, followed by upscaling of parameter fields to the model resolution. The method was tested using a 6‐hourly time step at four model resolutions (1.2, 2.4, 3.6, and 4.8 km), followed by a validation with discharge observations and a comparison with actual evapotranspiration (ETact) estimates from an independent model (DMET Land Surface Analysis Satellite Application Facility). Additionally, the scalability of parameter fields and simulated fluxes was tested. Validation of simulated discharges yielded Kling‐Gupta Efficiency (KGE) values ranging from 0.6 to 0.9, except for the Alps where a volume bias caused lower performance. Catchment‐averaged temporal ETact dynamics were comparable with independent ET estimates (KGE ≈ 0.7), although wflow_sbm model simulations were on average 115 mm yr−1 higher. Spatially, the two models were less in agreement (SPAEF = 0.10), especially around the Rhine valley. Consistent parameter fields were obtained, and by running the model at the different resolutions, preserved ETact fluxes were found across the scales. For recharge, fluxes were less consistent with relative errors around 30% for regions with high drainage densities. However, catchment‐averaged fluxes were better preserved. Routed discharge in headwaters was not consistent across scales, although simulations for the main Rhine River were. Better processing (scale independent) of the river and drainage network may overcome this issue.
Ectonucleotidase CD39 is highly expressed on ATLL cells and is responsible for their immunosuppressive function
Authors: Nagate Yasuhiro , Ezoe Sachiko , Fujita Jiro , Okuzaki Daisuke , Motooka Daisuke , Ishibashi Tomohiko , Ichii Michiko , Tanimura Akira , Kurashige Masako , Morii Eiichi , Fukushima Takuya , Suehiro Youko , Yokota Takafumi , Shibayama Hirohiko , Oritani Kenji , Kanakura Yuzuru 
Published: March 2020

AbstractAdult T-cell leukemia/lymphoma (ATLL) patients have an extremely poor prognosis, partly due to their immunosuppressive state. The majority of ATLL patients have leukemic cells with phenotype similar to Tregs, prompting suggestions that ATLL cells themselves have immunosuppressive functions. In this study, we detected CD39 expression on ATLL cells, particularly frequent on aggressive subtypes. CD39 and CD73 convert extracellular adenosine triphosphate (ATP) into adenosine, a key player in Tregs’ immunosuppression. In vitro culture, both CD39+ATLL cells and normal Tregs converted rapidly extracellular ATP to AMP, which was disturbed by CD39 inhibitors, and was negated in the CD39 knockout MJ cell line. The proliferation of cocultured CD4+/CD8+normal T cells was suppressed by CD39+MJ cells, but not by CD39 knockout MJ cells. Supplemented ATP was exhausted by an EG7-OVA T-cell line with stable CD39 induction, but not by mock. When these cell lines were subcutaneously transplanted into murine flanks, Poly(I:C) peritoneal administration reduced tumor size to 1/3 in mock-transplanted tumors, but not in CD39 induced tumors. Overall, we found that ATLL cells express CD39 at a high rate, and our results suggest that this helps ATLL cells escape antitumor immunity through the extracellular ATPDase-Adenosine cascade. These findings will guide future clinical strategies for ATLL treatment.
Regulation of Hippo signaling and triple negative breast cancer progression by an ubiquitin ligase RNF187
Authors: Wang Zhonghao , Kong Qiong , Su Peng , Duan Miao , Xue Min , Li Xin , Tang Jianing , Gao Zhitao , Wang Beibei , Li Zhongbo , Liu Yun , Yang Xiao , Cao Ruilin , Song Tingting , Wang Ke , Cai Yuqing , Wu Danfeng , Li Jinglei , Wu Gaosong , Guled Asha M. , Zhu Jian , Yan Cheng , Zhuang Ting 
Published: March 2020

AbstractBreast cancer is the most common malignancy for women worldwide, while Triple Negative Breast Cancer (TNBC) accounts for 20% in all patients. Compared with estrogen receptor positive breast cancer, which could be effectively controlled via endocrine therapy, TNBC is more aggressive and worse in prognosis. It is therefore urgent and necessary to develop a novel therapeutic strategy for TNBC treatment. Recent studies identified Hippo signaling is highly activated in TNBC, which could be a driving pathway for TNBC progression. In our study, we determine RNF187 as a negative regulator for Hippo signaling activation. RNF187 depletion significantly decreases cell migration and invasion capacity in TNBC. These effects could be rescued by further YAP depletion. Depletion of RNF187 increases the YAP protein level and Hippo signaling target genes, such as CTGF and CYR61 in TNBC. Immuno-precipitation assay shows that RNF187 associates with YAP, promoting its degradation possibly via inducing YAP K48-dependent poly-ubiquitination. Interestingly, Our clinical data reveals that RNF187 reversely correlates with YAP protein level and Hippo target genes. RNF187 tends to correlate with good prognosis in TNBC patients. Our study provides evidence to establish a proteolytic mechanism in regulation Hippo signaling activation in TNBC.
A novel stratification framework for predicting outcome in patients with prostate cancer
Authors: Luca Bogdan-Alexandru , Moulton Vincent , Ellis Christopher , Edwards Dylan R. , Campbell Colin , Cooper Rosalin A. , Clark Jeremy , Brewer Daniel S. , Cooper Colin S. 
Published: March 2020

Abstract
Background
Unsupervised learning methods, such as Hierarchical Cluster Analysis, are commonly used for the analysis of genomic platform data. Unfortunately, such approaches ignore the well-documented heterogeneous composition of prostate cancer samples. Our aim is to use more sophisticated analytical approaches to deconvolute the structure of prostate cancer transcriptome data, providing novel clinically actionable information for this disease.

Methods
We apply an unsupervised model called Latent Process Decomposition (LPD), which can handle heterogeneity within individual cancer samples, to genome-wide expression data from eight prostate cancer clinical series, including 1,785 malignant samples with the clinical endpoints of PSA failure and metastasis.

Results
We show that PSA failure is correlated with the level of an expression signature called DESNT (HR = 1.52, 95% CI = [1.36, 1.7], P = 9.0 × 10−14, Cox model), and that patients with a majority DESNT signature have an increased metastatic risk (X2 test, P = 0.0017, and P = 0.0019). In addition, we develop a stratification framework that incorporates DESNT and identifies three novel molecular subtypes of prostate cancer.

Conclusions
These results highlight the importance of using more complex approaches for the analysis of genomic data, may assist drug targeting, and have allowed the construction of a nomogram combining DESNT with other clinical factors for use in clinical management.
Identification of primordial germ cell-like cells as liver metastasis initiating cells in mouse tumour models
Authors: Liu Chunfang , Ma Zhan , Cai Zhen , Zhang Fengyu , Liu Cheng , Chen Tingjin , Peng Danni , Xu Xiaohong , Lin Hui-Kuan 
Published: March 2020

AbstractLiver metastasis, characterized by the spread of tumors to the liver from other areas, represents a deadly disease with poor prognosis. Currently, there is no effective therapeutic strategies and/or agents to combat liver metastasis primarily due to the insufficient understanding of liver metastasis. To develop a promising strategy for targeting liver metastasis, understanding of a cell origin responsible for liver metastasis and how this cell can be pharmacologically eliminated are therefore crucial. Using diverse tumor models including p53−/− genetic mouse model and syngeneic tumor models, we identified primordial germ cell (PGC)-like tumor cells, which are enriched in earliest liver micro-metastasis (up to 99%), as a cell origin of liver metastasis. PGC-like tumor cells formed earliest micro-metastasis in liver and gradually differentiated into non-PGC-like tumor cells to constitute late macro-metastasis in the course of tumor metastasis. The liver metastasis-initiating cells (PGC-like tumor cells) display cell renewal and differentiation capabilities, resemble primordial germ cells (PGCs) in morphology and PGC marker gene expression, and express higher level of the genes linked to metastasis and immune escape compared with non-PGC-like tumor cells. Of note, Stellarhigh PGC-like tumor cells, but not Stellarlow non-PGC-like cells, sorted from primary tumors of p53−/− mice readily form liver metastasis. Depletion of PGC-like tumor cells through genetic depletion of any of key germ cell genes impairs liver metastasis, while increased PGC-like tumor cells by SMAD2 knockout is correlated with markedly enhanced liver metastasis. Finally, we present the proof of principle evidence that pharmacologically targeting BMP pathways serves as a promising strategy to eliminate PGC-like tumor cells leading to abrogating liver metastasis. Collectively, our study identifies PGC-like tumor cells as a cell origin of liver metastasis, whose depletion by genetically targeting core PGC developmental genes or pharmacologically inhibiting BMP pathways serves a promising strategy for targeting liver metastasis.
Epidemiological data from the COVID-19 outbreak, real-time case information
Authors: Xu Bo , Gutierrez Bernardo , Mekaru Sumiko , Sewalk Kara , Goodwin Lauren , Loskill Alyssa , Cohn Emily L. , Hswen Yulin , Hill Sarah C. , Cobo Maria M. , Zarebski Alexander E. , Li Sabrina , Wu Chieh-Hsi , Hulland Erin , Morgan Julia D. , Wang Lin , O’Brien Katelynn , Scarpino Samuel V. , Brownstein John S. , Pybus Oliver G. , Pigott David M. , Kraemer Moritz U. G. 
Published: March 2020

AbstractCases of a novel coronavirus were first reported in Wuhan, Hubei province, China, in December 2019 and have since spread across the world. Epidemiological studies have indicated human-to-human transmission in China and elsewhere. To aid the analysis and tracking of the COVID-19 epidemic we collected and curated individual-level data from national, provincial, and municipal health reports, as well as additional information from online reports. All data are geo-coded and, where available, include symptoms, key dates (date of onset, admission, and confirmation), and travel history. The generation of detailed, real-time, and robust data for emerging disease outbreaks is important and can help to generate robust evidence that will support and inform public health decision making.
99mTc-labeled monosaccharide kits: development methods and quality control
Authors: Stasyuk Elena , Sкuridin Viktor , Rogov Alexander , Zelchan Roman , Sadkin Vladimir , Varlamova Natalya , Nestеrov Evgeny 
Published: March 2020

AbstractThe paper presents the procedure for planning an experiment to create standard sets of reagents for a technetium-99m generator based on glucose derivatives. All stages are presented from researching the required quantities of a substance, a reducing agent, a stabilizer and auxiliary components to developing lyophilized kits and conducting quality control. The radiochemical purity of radiopharmaceuticals prepared on the basis of the developed kits ranged from 90.0 to 99.0%. We also showed the functional suitability of the developed preparations on C57B1/6j mice with an implanted malignant tumor - Lewis lung carcinoma.
Theoretical insights into excited-state hydrogen bonding effects and intramolecular proton transfer (ESIPT) mechanism for BTS system
Authors: Wang Jiemin , Liu Qiang , Yang Dapeng 
Published: March 2020

AbstractIn this work, N,N’-bis(salicylidene)-(2-(3′,4′-diaminophenyl)benzothiazole) (named as “BTS”) system was studied about its excited-state intramolecular proton transfer (ESIPT) process. The analyses about reduced density gradient (RDG) reveal the formation of two intramolecular hydrogen bonds in BTS system. Bond lengths and angles, infrared (IR) vibrations as well as frontier molecular orbitals (MOs) using TDDFT method indicate that the strength of hydrogen bond should be enhanced in the S1 state. Particularly, hydrogen bond O1–H2···N3 undergoes larger variations compared with O4–H5···N6, which infers that hydrogen bond O1–H2···N3 may play a decisive role in the ESIPT process of BTS system. Given the two hydrogen bonds of BTS molecule, two types of potential energy curves have been constructed, which confirms that only single proton transfer process occurs due to lower energy barrier along with O1–H2···N3 rather than O4–H5···N6. This work not only presents a reasonable explanation for previous experiment, but also clarifies the specific ESIPT mechanism for BTS system.
Low FVC/TLC in Preserved Ratio Impaired Spirometry (PRISm) is associated with features of and progression to obstructive lung disease
Authors: Fortis Spyridon , Comellas Alejandro , Kim Victor , Casaburi Richard , Hokanson John E. , Crapo James D. , Silverman Edwin K. , Wan Emily S. 
Published: March 2020

AbstractOne quarter of individuals with Preserved Ratio Impaired Spirometry (PRISm) will develop airflow obstruction, but there are no established methods to identify these individuals. We examined the utility of FVC/TLC in identifying features of obstructive lung disease. The ratio of post-bronchodilator FVC and TLCCT from chest CT (FVC/TLCCT) among current and former smokers with PRISm (FEV1/FVC ≥ 0.7 and FEV1 < 80%) in COPDGene was used to stratify subjects into quartiles: very high, high, low, and very low. We examined the associations between FVC/TLCCT quartiles and (1) baseline characteristics, (2) respiratory exacerbations, (3) progression to COPD at 5 years, and (4) all-cause mortality. Among participants with PRISm at baseline (n = 1,131), the very low FVC/TLCCT quartile was associated with increased gas trapping and emphysema, and higher rates of progression to COPD at 5 years (36% versus 17%; p < 0.001) relative to the very high quartile. The very low FVC/TLCCT quartile was associated with increased total (IRR = 1.65; 95% CI [1.07–2.54]) and severe (IRR = 2.24; 95% CI [1.29–3.89]) respiratory exacerbations. Mortality was lower in the very high FVC/TLCCT quartile relative to the other quartiles combined. Reduced FVC/TLCCT ratio in PRISm is associated with increased symptoms, radiographic emphysema and gas trapping, exacerbations, and progression to COPD.
Comparative Evaluation of the Effectiveness of Novel Hyaluronic Acid-Polynucleotide Complex Dermal Filler
Authors: Kim Jong Hwan , Kwon Tae-Rin , Lee Sung Eun , Jang Yoo Na , Han Hye Sung , Mun Seog Kyun , Kim Beom Joon 
Published: March 2020

AbstractHA (Hyaluronic acid) filler, the most commonly used dermal filler, causes several side effects. HA-PN (Hyaluronic acid-Polynucleotide), a new composite filler, has excellent biocompatibility and induces tissue regeneration. In this study, we compare the efficacies and safety profiles of these fillers. The characteristics of HA and HA–PN fillers were compared using scanning electron microscopy and rheometry. No morphological difference was noted between the fillers. However, the latter had higher viscosity and elasticity values. The HA-PN filler induced higher cell migration than the HA filler in a wound healing assay. It was also found to stimulate better collagen synthesis in human and mouse fibroblasts. The HA and HA–PN fillers were injected into SKH1 hairless mice to determine changes in their volume for up to 24 weeks. Increased cell migration and collagen synthesis were observed in mice injected with the HA–PN complex filler. Although the safety and durability of the HA and HA–PN fillers were similar, the latter induced a lower transient receptor potential vanilloid 4 expression and caused less stimulation upon injection. In conclusion, HA–PN complex fillers can stimulate fibroblast growth and facilitate volume growth and skin regeneration.