bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of long‐term continuous positive airway pressure in the progression of obstructive sleep apnoea: A longitudinal cohort study
Authors: Sugiyama Ai , Shiota Satomi , Yanagihara Mariko , Nakayama Hideaki , Tsuiki Satoru , Hayashida Kenichi , Inoue Yuichi , Takahashi Kazuhisa 
Published: June 2021

SummaryRecent evidence suggests that short‐term obstructive sleep apnea (OSA) treatment could affect OSA pathogenesis such as ventilatory control. The aim of our present study was to identify the impact of long‐term treatment on the change in pathogenesis and natural progression of OSA. In a longitudinal analysis of a non‐obese cohort study, patients with OSA treated with either continuous positive airway pressure (CPAP) or an oral appliance (OA), interrupted their treatment for 1 week and underwent a polysomnography (PSG) off treatment that was compared with their initial PSG taken 5 years before treatment initiation. In all, 154 consecutive patients with OSA who were treated by CPAP using an auto‐titrating continuous positive airway pressure device (CPAP‐APAP) (n = 112), or by OA (n = 27) or were untreated (n = 15), PSG was performed twice with a median (range) follow‐up of 93 (60–176) months. Multivariate logistic regression showed that reduction of body mass index (BMI) and good treatment adherence to be significant predictors of favourable OSA progression, as represented by an improved or unchanged apnea–hypopnea index (AHI) (odds ratios were 5.14 and 2.89, respectively). Amongst the patients with an unchanged BMI and good CPAP‐APAP adherence (n = 55), the improvement in AHI was significantly associated with the decrease in supine non‐rapid eye movement‐AHI and mixed apnoea index/apnoea index, which are generally recognised to be determinants of ventilator instability. These findings suggest that not only weight but also treatment adherence are determinants in the natural progression of OSA severity.
The Algae Foundation® and Algae Technology Educational Consortium
Authors: Levine Ira A. , Gerk Cindy L. , Gómez Stephen M. , Nalley Jakob O. , Nalley Marissa M. 
Published: June 2021

AbstractThe Algae Foundation established in February 2013 has developed a diverse portfolio of algal‐based education and workforce development programs covering education levels from kindergarten through college, aquaculture extension, and free online courses. The Algae Foundation created the Algae Technology Educational Consortium (ATEC) with five major foci including community college certificate program in algae cultivation; community college curriculum adopted for algal biotechnology degree programs; Algal Massive Open Online Courses (Algal MOOCs); Algae Academy, a kindergarten to 12th grade STEM curriculum initiative; and aquaculture extension education through the Algae Cultivation Extension Short courses (ACES). The results include the education and training of over 102,000 students, aquaculturists, entrepreneurs, and bioeconomy‐based professionals aged 8–75 years in all 50 U.S. states and 66 countries. ATEC has completed agreements with 21 community colleges and universities located in Arizona, California, Connecticut, Hawaii, Louisiana, Maine, New Mexico, North Carolina, Oregon, Texas, and Washington. The first ATEC‐sponsored certificate degree program graduation was in May 2018. The Algae MOOC #1 has had over 15,752 students enrolled. ATEC initiated the Algae Academy in spring 2016 in Carlsbad, CA, and expanded to serving over 34,000 students in 46 states during the academic year 2019–2020. ACES has enrolled over 1,550 students from 66 countries.
Error, consistency and triviality
Authors: Tiefensee Christine , Wheeler Gregory 
Published: June 2021

AbstractIn this paper, we present a new semantic challenge to the moral error theory. Its first component calls upon moral error theorists to deliver a deontic semantics that is consistent with the error‐theoretic denial of moral truths by returning the truth‐value false to all moral deontic sentences. We call this the ‘consistency challenge’ to the moral error theory. Its second component demands that error theorists explain in which way moral deontic assertions can be seen to differ in meaning despite necessarily sharing the same intension. We call this the ‘triviality challenge’ to the moral error theory. Error theorists can either meet the consistency challenge or the triviality challenge, we argue, but are hard pressed to meet both.
An ethylene‐hypersensitive methionine sulfoxide reductase regulated by NAC transcription factors increases methionine pool size and ethylene production during kiwifruit ripening
Authors: Fu Bei‐ling , Wang Wen‐qiu , Liu Xiao‐fen , Duan Xue‐wu , Allan Andrew C. , Grierson Donald , Yin Xue‐ren 
Published: June 2021

Summary

Ethylene plays an important role in regulating fruit ripening by triggering dynamic changes in expression of ripening‐associated genes, but the functions of many of these genes are still unknown.

Here, a methionine sulfoxide reductase gene (AdMsrB1) was identified by transcriptomics‐based analysis as the gene most responsive to ethylene treatment in ripening kiwifruit.

The AdMsrB1 protein exhibits a stereospecific activity toward the oxidative stress‐induced R enantiomer of methionine sulfoxide (MetSO), reducing it to methionine (Met). Stable overexpression of AdMsrB1 in kiwifruit significantly increased the content of free Met and 1‐aminocyclopropane‐1‐carboxylic acid (ACC), the immediate precursor of ethylene, and increased ethylene production. Dual‐luciferase assays indicated that the AdMsrB1 promoter was not directly upregulated by ethylene treatment but was modulated by two ethylene‐inducible NAM/ATAF/CUC transcription factors (AdNAC2 and AdNAC72) that bind directly to the AdMsrB1 promoter. Overexpression of AdNAC72 in kiwifruit not only enhanced AdMsrB1 expression, but also increased free Met and ACC content and ethylene production rates.

This finding establishes an unexpected regulatory loop that enhances ethylene production and the concentration of its biosynthetic intermediates.
Iron isotopes as an ore‐fluid tracer: Case study of Qingchengzi Pb‐Zn‐Au(‐Ag) orefield in Liaoning, NE China
Authors: Li Dedong , Wang Yuwang , Wang Jingbin , Lai Chunkit , Qiu Jinzhu , Wang Wei , Li Shenghui , Zhang Zhichao 
Published: June 2021

AbstractThe Qingchengzi Pb‐Zn‐Au (‐Ag) orefield (eastern Liaoning province, NE China) is located in the northeastern margin of the North China Craton. The unconventional Fe isotopes of pyrites were analyzed to unravel the ore‐material source and migration pathway of the ore fluids. Pyrite samples of ores and wallrocks from various deposits in the orefield were collected and the solutions were analyzed by MC‐ICP‐MS. The results show that most pyrite samples contain heavier Fe isotopes than the international pyrite standard IRMM‐014. Within a particular deposit, Fe isotopes become lighter with depth. For example, the pyrite δ56Fe values drop from 0.216 ~ 0.408‰ (150‐m level) to −0.284 to −0.132‰ (210‐m level) at the Zhenzigou deposit. Gold deposits in the orefield also have similar features: At Baiyun (Huangdianzi), the pyrite δ56Fe values (0.394 ~ 0.627‰) of the silicic‐/potassic‐altered rock‐type ore (130‐m level) are significantly higher than that (0.359‰) of the quartz vein‐type ore (440‐m level). The lamprophyre δ56Fe values from different deposits are largely similar (0.040 ~ 0.024‰), whereas those in the wallrocks vary considerably (0.144 ~ 1.238‰). Compiling the pyrite δ56Fe values from many important sedimentary/metamorphic rock units in the region and magmatic‐hydrothermal deposits around the world, we concluded that the Qingchengzi Pb‐Zn‐Au(‐Ag) deposits belong to intrusion‐related magmatic‐hydrothermal type. The spatial fluid isotope variation pattern, and the fact that early‐formed sulfides have lighter isotopes than later ones, suggest that the Qingchengzi ore fluids may have originated from Zhenzigou‐Diannan (hydrothermal center) and outflown to Xiaotongjiapuzi, Gujiapuzi‐Baiyun and Erdao‐Xiquegou areas. The spatial fluid isotope variation pattern also suggests another possible hydrothermal center at Baiyun‐Gujiapuzi. The ability to identify hydrothermal center(s) and delineate fluid migration pathways suggests that pyrite Fe isotopes can serve as a tool for precious and base metals prospecting.
The cultural politics of new Tibetan entrepreneurship in contemporary China: Valorisation and the question of neoliberalism
Authors: Yeh Emily T. 
Published: June 2021

AbstractOver the past decade, new forms of Tibetan entrepreneurship have emerged and proliferated in China, at the intersection of a national push for entrepreneurship in response to a slowing economy, the closure of non‐governmental organisations in Tibetan areas, declining state‐sector employment, and state concerns about stability. This paper explores the rise of these new Tibetan entrepreneurs in relation to two inter‐related concerns. First, it contributes to geographers’ calls for comparative studies of culturally specific meanings of entrepreneurship across the Global South. It explores the cultural politics of Tibetan entrepreneurship – active debates about what it means to be a proper Tibetan, in terms of religious commitments and cultural pride, in relation to money‐making activities. Second, it analyses these in relation to critiques of neoliberal subjectivities associated with entrepreneurship. One of the key themes of Tibetan entrepreneurship is the effort to create economic value in the service of cultural value and a sense of self‐worth for Tibetans living in rural areas. Thus, elements of the neoliberal self are sutured together with a sense of responsibility to Tibetan communities and historically sedimented idioms to form an entrepreneurial subjectivity that is broadly oriented to the project of revalorising Tibetan places and people.
Analysis on In-Plane 2:2:1 Internal Resonance of a Complex Cable-Stayed Bridge System Under External Harmonic Excitation
Authors: Kang Houjun , Guo Tieding , Zhu Weidong 
Published: June 2021

AbstractNonlinear dynamic analysis of a cable-stayed bridge has been a hot topic due to its structural flexibility. Based on integro-partial differential equations of a double-cable-stayed shallow-arch model, in-plane 2:2:1 internal resonance among three first in-plane modes of two cables and a shallow arch under external primary or subharmonic resonance is considered. Galerkin's method and the method of multiple scales are used to derive averaged equations of this cable-stayed bridge system. Nonlinear dynamic behaviors of the system are investigated via numerical simulation. Results show rich nonlinear phenomena of the cable-stayed bridge system and some new phenomena are observed. Two identical cables that are symmetrically located above the shallow arch can have different dynamic behaviors even when initial conditions of the system are symmetrically given. Two cables with some differences between their parameters can exhibit either softening or hardening characteristics.
Acceleration and Jerk After a Jump Stabilization Task in Individuals With and Without Chronic Ankle Instability
Authors: Kosik Kyle B. , Lucas Kathryn , Hoch Matthew C. , Hartzell Jacob T. , Bain Katherine A. , Gribble Phillip A. 
Published: June 2021

Studies have demonstrated that individuals with chronic ankle instability (CAI) have diminished dynamic stability. Jerk-based measures have been utilized to examine dynamic balance because of their ability to quantify changes in acceleration and may provide an understanding of the postural corrections that occur during stabilizing following a jumping task. The purpose of this study was to compare acceleration and jerk following a jump stabilization task between individuals with CAI and the uninjured controls. Thirty-nine participants volunteered to participate in this case control study. Participants completed a jump stabilization task requiring them to jump off 2 feet, touch a marker set at 50% of their maximal vertical jump height, land on a single limb, and maintain balance for 3 seconds. Acceleration was calculated as the second derivative, and jerk was calculated as the third derivative of the displacement of the resultant vector position. Participants with CAI had greater acceleration (mean difference = 55.6 cm/s2; 95% confidence interval, 10.3 to 100.90; P = .017) and jerk compared with the uninjured controls (mean difference = 1804.5 cm/s3; 95% confidence interval, 98.7 to 3510.3; P = .039). These results suggest that individuals with CAI made faster and more frequent active postural control corrections to regain balance following a jump compared with the uninjured controls.
The Impact of a Randomized Controlled Trial Testing the Implementation of Function-Focused Care in Assisted Living on Resident Falls, Hospitalizations, and Nursing Home Transfers
Authors: Resnick Barbara , Boltz Marie , Galik Elizabeth , Zhu Shijun 
Published: June 2021

The purpose of this study was to test the impact of function-focused care on adverse outcomes in assisted living. This was a randomized trial including 85 settings. The age of the 794 recruited participants was 89.48 (SD = 7.43) years, the majority was female (n = 561, 71%) and White (n = 771, 97%). The percentage of residents in the treatment group experiencing a fall decreased at 12 months from 26% to 20% and the control group increased from 24% to 25%,p = .02. A greater percentage of residents in the treatment group transferred to nursing facilities at 4 months (4–1% in control vs. 4–5% in treatment,p = .02) and 12 months (4–2% in control and 4–7% in treatment,p = .01). There was no treatment effect on emergency room or hospital transfers. The findings support the safety of function-focused care related to falls and need for hospital transfers.
Efficacy of a carrageenan gel in preventing anal human papillomavirus (HPV) infection: interim analysis of the Lubricant Investigation in Men to Inhibit Transmission of HPV Infection (LIMIT-HPV) randomised controlled trial
Authors: Laurie Cassandra , El-Zein Mariam , Tota Joseph E , Khosrow-Khavar Farzin , Tellier Pierre-Paul , Coutlée François , de Pokomandy Alexandra , Franco Eduardo L 
Published: June 2021

BackgroundCarrageenan, a non-toxic gelling agent derived from red algae, has potent anti-human papillomavirus (HPV) activity in in vitro and animal studies. We assessed, in an interim analysis, the efficacy of a carrageenan-based gel in reducing the risk of new detections of anal HPV among gay, bisexual and other men who have sex with men (gbMSM).MethodsThe LIMIT-HPV study (Lubricant Investigation in Men to Inhibit Transmission of HPV Infection) is a phase IIb, double-blind, placebo-controlled randomised controlled trial conducted in Montreal, Canada. gbMSM were randomly assigned (1:1) to receive a carrageenan-based or placebo gel. Participants were instructed to apply the gel to the anus, condom and/or partners’ penis before and—as required—during receptive anal intercourse. Questionnaire data and anal samples were collected at 0, 1, 2, 3, 6, 9 and 12 months. We estimated new detections of anal HPV infection(s) detected via Linear Array using Cox proportional hazards models.ResultsParticipants recruited from February 2016 to December 2019 were randomly assigned to the carrageenan (n=127) or placebo (n=128) arm. The efficacy and safety analyses included 201 and 210 participants. The median follow-up time was 7.6 months (range: 0–28.5) in the carrageenan group and 9.3 months (range: 0–40.7) in the placebo group. The HR for new detections was 1.21 (95% CI 0.86 to 1.70): 69.4% and 65.1% new detections of HPV in the carrageenan and placebo arms, respectively. More adverse events were reported in the carrageenan (59.8%) compared with the placebo (39.8%) arm.ConclusionsThe interim analysis did not demonstrate a protective effect of carrageenan on the risk of new detections of anal HPV infection among gbMSM. Carrageenan gel use was associated with a higher proportion of adverse events. Given these findings and the (assumed) low probability that a beneficial effect would be found by the study’s end, the trial was terminated as recommended by the Data Safety and Monitoring Board.Trial registration numberNCT02354144.
Transcriptomic analysis reveals anthocyanin biosynthesis regulation in blueberry (Vaccinium ashei) fruit
Authors: Gao Xuan , Chen Qiang , Yang Yan , Zhu Bo , Xiao Jiaxin 
Published: June 2021

Blueberry (Vaccinium ashei) is a popular fruit due to its high anthocyanin content. This study aimed to analyze the transcriptome profile of V. ashei cv. ‘Brightwell’ fruits at different stages of development. A total of 314.26 GB of clean data were obtained and de novo assembled into 254 196 unigenes. In comparisons between the early and late stages of fruit ripening, 27 genes (including PAL, CHS, F3H, F3′H, F3′5′H, LDOX, etc.) were found to cover the main steps in the anthocyanin biosynthesis pathway. Most of these genes were highly expressed in the late stage of fruit development, suggesting that anthocyanins mainly accumulate in the late stage. During the late stage of fruit development, most structural and regulatory genes such as F3′5′H and F3′H, which are involved in the anthocyanin biosynthetic pathway, were upregulated, causing the fruit to turn blue. Decreased expression of a large number of chloroplast-related genes during the fruit ripening period could explain why the green fruit color fades over time. Additionally, abscisic acid and ethylene may play positive roles in promoting fruit ripening and anthocyanin accumulation. This research reveals the transcriptomic characteristics of immature and mature fruits and enhances our understanding of the molecular mechanisms of anthocyanin biosynthesis and accumulation in blueberry fruit.
Predictors and predictands of linear response in spatially extended systems
Authors: Tomasini Umberto Maria , Lucarini Valerio 
Published: June 2021

AbstractThe goal of response theory, in each of its many statistical mechanical formulations, is to predict the perturbed response of a system from the knowledge of the unperturbed state and of the applied perturbation. A new recent angle on the problem focuses on providing a method to perform predictions of the change in one observable of the system using the change in a second observable as a surrogate for the actual forcing. Such a viewpoint tries to address the very relevant problem of causal links within complex system when only incomplete information is available. We present here a method for quantifying and ranking the predictive ability of observables and use it to investigate the response of a paradigmatic spatially extended system, the Lorenz ’96 model. We perturb locally the system and we then study to what extent a given local observable can predict the behaviour of a separate local observable. We show that this approach can reveal insights on the way a signal propagates inside the system. We also show that the procedure becomes more efficient if one considers multiple acting forcings and, correspondingly, multiple observables as predictors of the observable of interest.
Radiotherapy and Immunotherapy Combinations in the Treatment of Patients with Metastatic Disease: Current Status and Future Focus
Authors: Turchan William Tyler , Pitroda Sean P. , Weichselbaum Ralph R. 
Published: June 2021

AbstractRadiotherapy and immunotherapy benefit subsets of patients with metastatic cancer. Here, we review selected laboratory and clinical studies investigating the utility of combining radiotherapy and immunotherapy in metastatic patients. We examine potential approaches to increase the therapeutic ratio of radioimmunotherapy in the treatment of metastatic cancers moving forward.
ONC212 is a Novel Mitocan Acting Synergistically with Glycolysis Inhibition in Pancreatic Cancer
Authors: Ferrarini Isacco , Louie Anna , Zhou Lanlan , El-Deiry Wafik S. 
Published: June 2021

Abstract
ONC212 is a fluorinated imipridone with preclinical efficacy against pancreatic and other malignancies. Although mitochondrial protease ClpP was identified as an ONC212-binding target, the mechanism leading to cancer cell death is incompletely understood. We investigated mitochondrial dysfunction and metabolic rewiring triggered by ONC212 in pancreatic cancer, a deadly malignancy with an urgent need for novel therapeutics. We found ClpP is expressed in pancreatic cancer cells and is required for ONC212 cytotoxicity. ClpX, the regulatory binding partner of ClpP, is suppressed upon ONC212 treatment. Immunoblotting and extracellular flux analysis showed ONC212 impairs oxidative phosphorylation (OXPHOS) with decrease in mitochondrial-derived ATP production. Although collapse of mitochondrial function is observed across ONC212-treated cell lines, only OXPHOS-dependent cells undergo apoptosis. Cells relying on glycolysis undergo growth arrest and upregulate glucose catabolism to prevent ERK1/2 inhibition and apoptosis. Glucose restriction or combination with glycolytic inhibitor 2-deoxy-D-glucose synergize with ONC212 and promote apoptosis in vitro and in vivo. Thus, ONC212 is a novel mitocan targeting oxidative metabolism in pancreatic cancer, leading to different cellular outcomes based on divergent metabolic programs.
Anti-Glypican-1 Antibody–drug Conjugate as Potential Therapy Against Tumor Cells and Tumor Vasculature for Glypican-1–Positive Cholangiocarcinoma
Authors: Yokota Keiichiro , Serada Satoshi , Tsujii Shigehiro , Toya Keisuke , Takahashi Tsuyoshi , Matsunaga Takashi , Fujimoto Minoru , Uemura Sunao , Namikawa Tsutomu , Murakami Ichiro , Kobayashi Shogo , Eguchi Hidetoshi , Doki Yuichiro , Hanazaki Kazuhiro , Naka Tetsuji 
Published: June 2021

AbstractCholangiocarcinoma is a highly malignant cancer. Many patients need systemic chemotherapy to prevent tumor development and recurrence; however, their prognosis is poor due to the lack of effective therapy. Therefore, a new treatment option is urgently required. We recently identified glypican-1 (GPC1) as a novel cancer antigen of esophageal squamous cell carcinoma. We also demonstrated the efficacy and safety of GPC1-targeted ADC (GPC1–ADC) conjugating anti-GPC1 mAb possessing high internalization activity with monomethyl auristatin F (MMAF), which is a potent tubulin polymerizing inhibitor. In this study, we confirmed that GPC1 was highly expressed in cholangiocarcinoma cells and tissues. IHC analysis of 49 extrahepatic cholangiocarcinoma patient tumor specimens revealed high expression of GPC1 in 47% of patients. These patients demonstrated significantly poorer prognosis compared with the low-expression group in terms of disease-free survival and overall survival (P &lt; 0.05). GPC1 was also expressed in tumor vessels of cholangiocarcinoma, but not on the vessels of nontumor tissues. MMAF-conjugated GPC1–ADC showed potent tumor growth inhibition against GPC1-positive cholangiocarcinoma cells in vitro and in vivo. In a GPC1 knockout xenograft model, GPC1–ADC partially inhibited tumor growth. Vascular endothelial cells in tumor tissues of GPC1-negative xenograft mice expressed GPC1 and were arrested in the G2–M phase of cell cycle by GPC1–ADC. GPC1–ADC exhibits direct as well as indirect antitumor effects via inhibition of tumor angiogenesis. Our preclinical data highlight GPC1–ADC as a promising therapy for GPC1-positive cholangiocarcinoma.