bluuebunny/crossref_metadata_2025 huggingface dataset:
The cost of improving care: a multisite economic analysis of hospital resource use for implementing recommended postpartum contraception programmes
Authors: Ling Vivian B , Levi Erika E , Harrington Amy R , Zite Nikki B , Rivas Saul D , Dalton Vanessa K , Smith Roger , Moniz Michelle H
Published: September 2020

Background

The costs of quality improvement efforts in real-world settings are often unquantified. Better understanding could guide appropriate resource utilisation and drive efficiency. Immediate postpartum contraceptive care (ie, placement of an intrauterine device or contraceptive implant during hospitalisation for childbirth) represents an excellent case study for examining costs, because recommended services are largely unavailable and adoption requires significant effort. We therefore evaluated the cost of implementing immediate postpartum contraceptive services at four academic centres and one private hospital in USA.

Methods

In this mixed-methods cost analysis, implementation activities were retrospectively identified using standardised data collection. Activities were categorised as preimplementation activities (infrastructure building, tool creation and stakeholder engagement) or execution activities (workforce training and process refinement). Costs were assigned based on national median salaries for the roles of individuals involved. Cross-case comparison and rapid qualitative analysis guided by the Consolidated Framework for Implementation Research were used to identify factors driving cost variation observed across sites.

Results

On average, implementation activities required 204 hours (range 119–368), with this time costing $14 433.94 (range $9955.61–$23 690.49), and involving 9 (range 7–11) key team members per site. Preimplementation activities required more resources than execution activities (preimplementation: average 173 hours, $11 573.25; execution: average 31 hours, $2860.67). Sites that used lower-cost employees (eg, shifting tasks from a physician to a project manager) observed lower costs per hour for implementation activities. Implementation activities and costs were associated with local contextual factors, including stakeholder acceptance, integration of employees and infrastructure readiness for the change effort.

Conclusions

Our findings provide the first estimates of health system costs for adopting recommended contraceptive care in maternity units in USA. More broadly, our findings suggest that the budget impact of improvement efforts may vary widely depending on local context.
Frequency and prognostic impact of right ventricular involvement in acute myocardial infarction
Authors: Stiermaier Thomas , Backhaus Sören J , Matz Jonas , Koschalka Alexander , Kowallick Johannes , de Waha-Thiele Suzanne , Desch Steffen , Gutberlet Matthias , Hasenfuß Gerd , Thiele Holger , Eitel Ingo , Schuster Andreas
Published: September 2020

Objective

Right ventricular (RV) involvement complicating myocardial infarction (MI) is thought to impact prognosis, but potent RV markers for risk stratification are lacking. Therefore, the aim of this trial was to assess the frequency and prognostic implications of concomitant structural and functional RV injury in MI.

Methods

Cardiac magnetic resonance (CMR) was performed in 1235 patients with MI (ST-elevation myocardial infarction: n=795; non-STEMI: n=440) 3 days after reperfusion by primary percutaneous coronary intervention. Central core laboratory-masked analyses included structural (oedema representing reversible ischaemia, irreversible infarction, microvascular obstruction (MVO)) and functional (ejection fraction, global longitudinal strain (GLS)) RV alterations. The clinical end point was the 12-month rate of major adverse cardiac events (MACE).

Results

RV ischaemia and infarction were observed in 19.6% and 12.1% of patients, respectively, suggesting complete myocardial salvage in one-third of patients. RV ischaemia was associated with a significantly increased risk of MACE (10.1% vs 6.2%; p=0.035), while patients with RV infarction showed only numerically increased event rates (p=0.075). RV MVO was observed in 2.4% and not linked to outcome (p=0.894). Stratification according to median RV GLS (10.2% vs 3.8%; p<0.001) but not RV ejection fraction (p=0.175) resulted in elevated MACE rates. Multivariable analysis including clinical and left ventricular MI characteristics identified RV GLS as an independent predictor of outcome (HR 1.05, 95% CI 1.00 to 1.09; p=0.034) in addition to age (p=0.001), Killip class (p=0.020) and left ventricular GLS (p=0.001), while RV ischaemia was not independently associated with outcome.

Conclusions

RV GLS is a predictor of postinfarction adverse events over and above established risk factors, while structural RV involvement was not independently associated with outcome.
Lack of myeloid cell infiltration as an acquired resistance strategy to immunotherapy
Authors: Beyranvand Nejad Elham , Labrie Camilla , Abdulrahman Ziena , van Elsas Marit J , Rademaker Eva , Kleinovink Jan Willem , van der Sluis Tetje C , van Duikeren Suzanne , Teunisse Amina F A.S , Jochemsen Aart G , Oosting Jan , de Miranda Noel F C C , Van Hall Thorbald , Arens Ramon , van der Burg Sjoerd H
Published: September 2020

Background

Immunotherapy of cancer is successful but tumor regression often is incomplete and followed by escape. Understanding the mechanisms underlying this acquired resistance will aid the development of more effective treatments.

Methods

We exploited a mouse model where tumor-specific therapeutic vaccination results in tumor regression, followed by local recurrence and resistance. In depth studies on systemic, local and tumor intrinsic changes were performed with flow and mass cytometry, immunohistochemistry, transcriptomics and several perturbation studies with inhibitors or agonistic antibodies in mice. Main findings were recapitulated in vaccinated patients.

Results

Full tumor regression and cure of tumor-bearing mice is dependent on the magnitude of the vaccine-induced T-cell response. Recurrence of tumors did not involve classical immune escape mechanisms, such as antigen-presentation alterations, immune checkpoint expression, resistance to killing or local immune suppression. However, the recurrent tumors displayed a changed transcriptome with alterations in p53, tumor necrosis factor-α and transforming growth factor-β signaling pathways and they became immunologically cold. Remarkably, ex vivo cell-sorted recurrent tumors, directly reinjected in naïve hosts retained their resistance to vaccination despite a strong infiltration with tumor-specific CD8+T cells, similar to that of vaccine-responsive tumors. The influx of inflammatory mature myeloid effector cells in the resistant tumors, however, was impaired and this turned out to be the underlying mechanisms as restoration of inflammatory myeloid cell infiltration reinstated the sensitivity of these refractory tumors to vaccination. Notably, impaired myeloid cell infiltration after vaccination was also associated with vaccine resistance in patients.

Conclusion

An immunotherapy-induced disability of tumor cells to attract innate myeloid effector cells formed a major mechanism underlying immune escape and acquired resistance. These data not only stresses the importance of myeloid effector cells during immunotherapy but also demands for new studies to harness their tumoricidal activities.
Pre-exposure HIV prophylaxis (PrEP) among transgender women: 3 years of follow-up in a university hospital in Paris
Authors: Isernia Valentina , Phung Bao , Lepretre Annie Marie , Azadi Bahar , Rincon Giovanna , Zelie Julia , Le Gac Sylvie , Deprez Andres , Michard Florence , Yazdanpanah Yazdan , Ghosn Jade
Published: September 2020

Objectives

The principal outcome was to describe clinical characteristics of a transgender male-to-female (TGW) cohort followed for pre-exposure HIV prophylaxis (PrEP).

Introduction

Few efforts and preventive interventions have targeted transgender population, despite them being at great risk of HIV infection.

Methods

This was a retrospective transgender male-to-female (TGW) cohort followed for PrEP at Bichat Hospital Sexual Health Clinic between February 2016 and January 2019.

The principal outcome was to describe clinical characteristics of this TGW population: modalities of PrEP uptake, treatment adherence and tolerance, sanitary system retention, hormonal therapy and STIs.

Data about age, ethnicity, language, sex work and sanitary healthcare insurance coverage were also collected.

Results

Forty-nine TGW were included, with a median age of 33 years; 43/49 (87.7%) were from South America and 43/49 (87.7%) were sex workers. Forty-four 44/49 TGW (89.7%) had no regular healthcare insurance coverage. Nineteen out of 49 (38.7%) had a history of STI in the last 12 months. Hormone intake was reported in 16/49 (32.60%). PrEP with oral TDF/FTC was prescribed on a daily basis for 45/49 TG (91.8%). Two TGW discontinued PrEP for gastrointestinal intolerance. No case of renal toxicity or HIV seroconversion has been reported. Retention rate was high (71.4%), but average follow-up was 9 months.

Conclusions

Our data showed a very vulnerable population, with a high proportion of migrants, sex workers and with a low healthcare insurance coverage. Retention rate was high (71.4%). Further multi-component interventions are needed to improve global sex health approach, PreP follow-up and sanitary system retention among TGW population.
Computed tomography and magnetic resonance imaging findings in a dog with apocrine gland anal sac adenocarcinoma with vertebral canal metastasis
Authors: Kenny Dan , Lantzaki Vasiliki , Ayl Rodney , Barker David
Published: September 2020

A 10‐year‐old male neutered cocker spaniel was presented for further investigation of an enlarged sublumbar lymph node, which was cytologically consistent with epithelial cell malignancy. CT revealed marked left medial and internal iliac and mild lumbo‐aortic lymphadenomegaly. Surgical extirpation of the lymph nodes was performed, and histopathology was consistent with poorly differentiated carcinoma. Despite the absence of a discernible primary lesion, metastatic apocrine gland anal sac adenocarcinoma (AGASAC) was suspected and chemotherapy was started. Six days after starting chemotherapy, the patient developed acute‐onset paraparesis and trembling. MRI revealed a left‐sided extradural mass at the level of T11–T13. CT imaging revealed mild enlargement of multiple left sided lumbo‐aortic lymph nodes. The dog was euthanised 3 days later due to neurological deterioration. Postmortem examination confirmed a diagnosis of left AGASAC with local lymph node and T11–T13 vertebral canal metastasis.
Distribution and source of Pu in the sediments of the seas and estuaries of China—a review
Authors: Wang Ruirui , Liu Zhiyong
Published: September 2020

The coastal zone is the most concentrated area of human activities, and it is also the main accumulation zone of continental sediments, which is an ideal area for studying anthropocene sedimentary records. This study summarizes the distribution of 239+240Pu activity, 239+240Pu inventory, and 240Pu/239Pu atom ratios in the sediments of the seas and estuaries of China. Studies have shown that the distribution of 239+240Pu activity in sediments is mainly influenced by sediment properties and ocean current dynamics. Furthermore, 239+240Pu activity in sediment cores has obvious peak characteristics, which can be used in sediment dating. In fact, 240Pu/239Pu atom ratios indicate that the Pu in the sediments of the seas and estuaries of China mainly comes from global fallout and the Pacific Proving Grounds (PPG). Pu from the PPG enters the seas of China through the North Equatorial Current and Kuroshio intrusion current. And the contribution of Pu from the PPG in the East China Sea, the South China Sea, and the Yangtze estuary is over 40%. Moreover, Pu has been applied in the tracer of land-sea interactions and ocean dynamics, and it can be used as a background value to study the changes of Pu in the coastal zone of China in the future.
Valve morphogenesis in selected centric diatoms
Authors: Kaczmarska Irena , Ehrman James M. , Davidovich Nickolai A. , Davidovich Olga I. , Podunay Yulia A.
Published: September 2020

The traditional taxonomic affiliation of the diatom Ardissonea crystallina (C. Agardh) Grunow has been recently questioned, as it exhibits a mixture of polar centric and araphid pennate characters. Overall valve architecture and mode of sexual reproduction suggest that araphid pennates are its closest relatives. On the other hand, recovered molecular phylogenies consistently place it among the polar centrics. Our investigation of the earliest stages of valve morphogenesis, formation of the basal silica layer, adds to the argument that A. crystallina is indeed a polar centric diatom. We compared developmental stages in A. crystallina with unequivocally centric diatoms (non-polar Hyalodiscus stelliger and polar Biddulphia tridens) and published literature for araphid pennates and determined that A. crystallina has evolved an apparently unique mode of valve development. The significance of valve morphogenesis in better understanding diatom evolution and diversification is discussed.
Differential infestation of juvenile Pacific salmon by parasitic sea lice in British Columbia, Canada
Authors: Brookson Cole B. , Krkošek Martin , Hunt Brian P.V. , Johnson Brett T. , Rogers Luke A. , Godwin Sean. C.
Published: September 2020

Fraser River Pacific salmon have declined in recent decades, possibly from parasitism by sea lice (Caligus clemensi and Lepeophtheirus salmonis). We describe the abundance of both louse species infesting co-migrating juvenile pink (Oncorhynchus gorbuscha), chum (Oncorhynchus keta), and sockeye (Oncorhynchus nerka) salmon over 5 years in the Discovery Islands and Johnstone Strait, British Columbia. The generalist louse, C. clemensi, was 5, 7, and 39 times more abundant than the salmonid specialist, L. salmonis, on pink, chum, and sockeye salmon, respectively. Caligus clemensi abundance was higher on pink salmon (0.45, 95% CI: 0.38–0.55) and sockeye (0.39, 95% CI: 0.33–0.47) than on chum salmon. Lepeophtheirus salmonis abundance was highest on pink salmon (0.09, 95% CI = 0.06–0.15). Caligus clemensi had higher abundances in Johnstone Strait than in the Discovery Islands. These results suggest differences in host specialization and transmission dynamics between louse species. Because both lice infest farmed salmon, but only C. clemensi infests Pacific herring (Clupea pallasii), conservation science and management regarding lice and Fraser River salmon should further consider C. clemensi and transmission from farmed salmon and wild herring.
Relative conservation value of Nova Scotia’s forests: forested wetlands as avian diversity hotspots
Authors: Brazner John , MacKinnon Frances
Published: September 2020

Nova Scotia’s forested landscapes are degraded and under stress. As the province moves toward an ecological forestry management approach, land managers need more complete information about the relative biodiversity value of various habitats in landscapes that they manage to fully assess conservation consequences of different management options. To begin assessing the relative conservation value of different forest types, we surveyed bird communities in 18 forested wetlands (wooded bogs, tall shrub swamps, and treed swamps), mature upland forest stands, and regenerating upland forest stands in western Nova Scotia during the breeding season in 2017 and 2018. There were distinct differences among the bird communities in each forest type. Bird species diversity, overall abundance, and abundance of several guilds and species of conservation concern were higher in forested wetlands than in mature and regenerating upland forests. Bogs and shrub swamps had the highest number of species with strong habitat affinities, but treed swamps and mature sites had unique suites of strongly associated species and guilds — several of conservation concern. Regenerating sites were occupied mainly by forest-edge species and conservation value was low. Our study highlights the importance of forested wetlands to bird conservation and supports the idea that forested wetlands are avian diversity hotspots.
Soybean (Glycine max) PHYTOCHROME-INTERACTION FACTOR 1 induced skotomorphogenesis and de-etiolation in Arabidopsis
Authors: Wang Tianliang , Wang Shuo , Zhang Jinhao , Yan Fan , Liu Yajing , Wang Ying , Zhao Lei , Wang Qingyu , Li Jingwen
Published: September 2020

Skotomorphogenesis occurs after germination and before excavation in plants. It inhibits excessive absorbed energy in cells and can prevent the lethal photooxidative damage caused by transitioning from skotomorphogenesis to photomorphogenesis for light energy utilization. To investigate the mechanisms underlying photoreactions in soybean [Glycine max (L.) Merr.], we identified and isolated soybean phytochrome-interaction factor 1 (GmPIF1). A yeast two-hybrid (Y2H) assay showed that GmPIF1 interacted with photoactive PHYTOCHROME A (PHYA) and B (PHYB) in both soybean and Arabidopsis (GmPHYA, GmPHYB, AtPHYA, and AtPHYB). To analyze its function, we ectopically over-expressed GmPIF1 in wild type and pif1 mutant Arabidopsis. In etiolated seedlings, GmPIF1 caused hypocotyl elongation, cotyledon closed, apical hooks folded, and less accumulation of protochlorophyllide. In Y2H, GmPIF1 interacted with AtHDA15 that inhibited chlorophyll synthesis under dark conditions. After transition from darkness to white light, GmPIF1 promotes the reduction of photobleaching and induced de-etiolation. Moreover, GmPIF1 inhibited PHYA- and PHYB-mediated seed germination. Our findings increase our understanding of the regulatory network of light response in soybean and provide useful gene resources for soybean breeding in programs and genetics engineering.
An Application Specific Reconfigurable Architecture with Reduced Area and Static Memory Cells
Authors: Iqbal Muhammad Mazher , Parvez Husain , Hussain Fasahat , Rashid Muhammad
Published: September 2020

An Application Specific Inflexible FPGA (ASIF) is a tailored design, for a given group of known circuits, which is generated by extensively reducing the routing resources of an FPGA. In an ASIF, different dynamically reconfigurable application circuits are initially mapped and tested on an FPGA fabric. Subsequently, the FPGA fabric is reduced to achieve an efficient architecture for known application circuits. However, a large portion of ASIF is still occupied by fully flexible logic blocks, containing the same amount of area and SRAM memory cells, as found in a traditional FPGA. Thus, here lies a potential to further optimize the logic blocks of an ASIF at the expense of removing or reducing their reconfigurability. This work optimizes the logic blocks of an ASIF through the SRAM-Table sharing technique, without compromising their reconfigurability. Moreover, the routing channels of ASIF are further optimized by applying the Boolean functions (Gates) insertion technique. The applied techniques (SRAM-Table sharing and Boolean functions insertion) not only reduce the area, delay and power, but also minimize the reconfiguration time, bitstream size and the size of external memory required to store the bitstream of circuits. This optimized version of ASIF is termed as ASIF[Formula: see text]. Furthermore, an embedded FPGA in a System-on-Chip that requires the partial dynamic reconfiguration for known circuits, can be automatically reduced to an ASIF[Formula: see text]. It is found through experimental results that an ASIF[Formula: see text] is 4–9[Formula: see text] area-efficient and requires [Formula: see text] lesser number of SRAM cells, as compared to the previously proposed ASIF for a group of 2–5 circuits. It also achieves 34–53[Formula: see text] area saving as compared to a traditional FPGA.
DESIGN AND ANALYSIS OF NEW STENT PATTERNS FOR ENHANCED PERFORMANCE
Authors: PANNEERSELVAM NISANTHKUMAR , MUTHUSWAMY SREEKUMAR
Published: September 2020

Deploying a stent to restore blood flow in the coronary artery is very complicated, as its internal diameter is smaller than 3[Formula: see text]mm. It has already been proven that mechanical stresses induced on stent and artery during deployment make the placement of stent very difficult, besides the development of complications due to artery damage. Various stent designs have already been developed, especially in the metallic category. Still, there are possibilities for developing new stent designs and patterns to overcome the complexities of the existing models. Also, the technology of metallic stents can be carried forward towards the development of bioresorbable polymeric stents. In this work, three new stent cell designs (curvature, diamond, and oval) have been proposed to obtain better performance and life. The finite element method is utilized to explore the mechanical behavior of stent expansion and determine the biomechanical stresses imposed on the stent and artery during the stenting procedure. The results obtained have been compared with the available literature and found that the curvature cell design develops lower stresses and, hence, be suitable for better performance and life.
Arrhythmias Prediction Using an Hybrid Model Based on Convolutional Neural Network and Nonlinear Regression
Authors: Abdou Abdoul-Dalibou , Ngom Ndeye Fatou , Niang Oumar
Published: September 2020

In biomedical signal processing, artificial intelligence techniques are used for identifying and extracting relevant information. However, it lacks effective solutions based on machine learning for the prediction of cardiac arrhythmias. The heart diseases diagnosis rests essentially on the analysis of various properties of ECG signal. The arrhythmia is one of the most common heart diseases. A cardiac arrhythmia is a disturbance of the heart rhythm. It occurs when the heart beats too slowly, too fast or anarchically, with no apparent cause. The diagnosis of cardiac arrhythmias is based on the analysis of the ECG properties, especially, the durations (P, QRS, T), the amplitudes (P, Q, R, S, T), the intervals (PQ, QT, RR), the cardiac frequency and the rhythm. In this paper we propose a system of arrhythmias diagnosis assistance based on the analysis of the temporal and frequential properties of the ECG signal. After the features extraction step, the ECG properties are then used as input for a convolutional neural network to detect and classify the arrhythmias. Finally, the classification results are used to perform a prediction of arrhythmias with nonlinear regression model. The method is illustrated using the MIT-BIH database.
Effects of progressive Orff vocal therapy on BODE index and quality of life in patients with low lung function after non-small cell lung cancer surgery
Authors: Du Yijie , Su Mingyue , Xue Hongli , Ma Mengyu , Wu Xilong , Xue Hanyu , Yi Tao , Tang Zhao , Kong Qing , Xu Yizhe , Cao Yuxue
Published: September 2020

Objective: To explore the effect of Orff vocal therapy on BODE index and quality of life of patients with low lung function after non-small cell lung cancer surgery.

Methods: From March 2014 to March 2019, 231 patients with NSCLC postoperative (their pulmonary functions FEV1 [Formula: see text] of the expected value) in the Huashan Hospital, Fudan University were selected and randomly divided into observation groups and control group. On the basis of conventional treatment of NSCLC, the control group used lung rehabilitation training, and the observation group used the Orff music therapy. They carry out vocal and breath training step by step, using a combination of online and offline methods, 1[Formula: see text]h per day online interactive training, 2[Formula: see text]h of offline group vocal therapy once a week, continuous intervention for 12 months. The patient’s BODE index and FACT-L scores were monthly follow-up.

Results: Compared with the control group, the BODE index and FACT-L scores improved more significantly in the vocal therapy group ([Formula: see text]). Especially in the FEV1pred, family/society module and functional status module, the improvement was most significant, compared with the control group ([Formula: see text]). And the loss of follow-up rate in the vocal therapy group was lower than that in the lung rehabilitation group ([Formula: see text]).

Conclusion: Orff vocal therapy can improve the BODE index and quality of life of patients with low lung function after non-small cell lung cancer surgery, and its compliance and intervention effects are better than ordinary lung rehabilitation training.
Constant-Delay Enumeration for Nondeterministic Document Spanners
Authors: Amarilli Antoine , Bourhis Pierre , Mengel Stefan , Niewerth Matthias
Published: September 2020

One of the classical tasks in information extraction is to extract subparts of texts through regular expressions. In the database theory literature, this approach has been generalized and formalized as document spanners. In this model, extraction is performed by evaluating a particular kind of automata, called a sequential variable-set automaton (VA). The efficiency of this task is then measured in the context of enumeration algorithms: we first run a preprocessing phase computing a compact representation of the answers, and second we produce the results one after the other with a short time between consecutive answers, called the delay of the enumeration. Our goal is to have an algorithm that is tractable in combined complexity, i.e., in the sizes of the input document and the VA, while ensuring the best possible data complexity bounds in the input document size, i.e., a constant delay that does not depend on the document. We present such an algorithm for a variant of VAs called extended sequential VAs and give an experimental evaluation of this algorithm.
Intraspecific Genetic Variation and Species Interactions Contribute to Community Evolution
Authors: Whitham Thomas G. , Allan Gerard J. , Cooper Hillary F. , Shuster Stephen M.
Published: September 2020

Evolution has been viewed as occurring primarily through selection among individuals. We present a framework based on multilevel selection for evaluating evolutionary change from individuals to communities, with supporting empirical evidence. Essential to this evaluation is the role that interspecific indirect genetic effects play in shaping community organization, in generating variation among community phenotypes, and in creating community heritability. If communities vary in phenotype, and those phenotypes are heritable and subject to selection at multiple levels, then a community view of evolution must be merged with mainstream evolutionary theory. Rapid environmental change during the Anthropocene will require a better understanding of these evolutionary processes, especially selection acting at the community level, which has the potential to eliminate whole communities while favoring others.
Existence and Uniqueness of Positive Solutions for a New System of Fractional Differential Equations
Authors: Li Hongyu , Chen Yang
Published: September 2020

By virtue of a recent existing fixed point theorem of increasing φ−h,e-concave operator by Zhai and Wang, we consider the existence and uniqueness of positive solutions for a new system of Caputo-type fractional differential equations with Riemann–Stieltjes integral boundary conditions.
Electroacupuncture Alleviates Osteoarthritis by Suppressing NLRP3 Inflammasome Activation in Guinea Pigs
Authors: Wang Zhankui , Chen Mo , Wang Bo , Kang Wulin , Yu Hongchao , Li Xiaoqun , Dong Bo , Yuan Puwei
Published: September 2020

Osteoarthritis (OA) is an increasingly prevalent disease affecting synovial joints, which includes joint degeneration, inflammation, and joint pain. The activation of nucleotide‐binding and oligomerization domain‐like receptor containing protein 3 (NLRP3) could promote synovial inflammation. Previous studies have shown that electroacupuncture (EA) has potential anti‐inflammatory effect. However, the effect of EA treatment on OA remains unclear. The aim of this study was to investigate the effect of applied EA on OA and joint pain and its relationship with NLRP3 inflammasome. The Hartley guinea pigs with naturally occurring OA at age 18 months were chosen as the OA model and treated with EA for 4 weeks. Mechanical allodynia was quantified by using von Frey filaments. The expression of NLRP3 inflammasome and the downstream proinflammatory factors in the cartilage tissue were quantified. Our results showed that EA treatment significantly reduces mechanical allodynia, improves the articular cartilage structure, and decreases the fibrillation on the cartilage surface in guinea pigs with spontaneous osteoarthritis. Moreover, we also found that EA treatment attenuates the NLRP3 inflammasome activation and suppresses the protein expression levels of caspase‐1 and IL‐1β in the cartilage tissue. Our findings suggest that EA treatment attenuates OA and joint pain by suppressing NLRP3 inflammasome activation and support further investigation of the potential therapeutic tactics.
Safety and Efficacy of Ginkgo‐Damole and Nitroglycerin or Sodium Nitroprusside on Hypertensive Cerebropathies: A Meta‐Analysis
Authors: Peng Li , Zhao Wei-kun , Xu Tong-tong , Wu Qi , Lu Pan , Zhu Pan-pan , Zheng Xiao-ming
Published: September 2020

Objective. To systematically evaluate the safety and efficacy of ginko‐damole combined with nitroglycerin or unitary sodium nitroprusside on hypertensive cerebropathy. Methods. Four Chinese databases (VIP, CBM, Wanfang database, and CNKI database) and three English databases (Cochrane, PubMed, and EMBASE) were used to screen randomised controlled trials (RCTs) on treatments of hypertensive cerebropathy using both ginko‐damole and nitroglycerin or unitary sodium nitroprusside. Outcomes included clinical effect, blood pressure after treatment, and adverse effects. These indicators were then analysed statistically using the RevMan 5.3 and Stata 12.0 software. Results. Altogether, 16 RCTs including 1507 patients with hypertensive cerebropathy were included in the present meta‐analysis, of which, 755 patients treated with combined ginko‐damole and nitroglycerin were included in the observation group and 752 patients treated with sodium nitroprusside were included in the control group. The curative effect of the observation group was significantly better than that of the control group (RR: 1.115 [1.077, 1.155], p < 0.05). DBPs of the observation and control groups were both lower after treatment, and no significant difference was observed between the observation and control groups (MD: −1.072 [−2.578, 0.434], p > 0.05). SBPs in the observation group were significantly lower than those in the control group (MD: −2.842 [−5.222, −0.462], p < 0.05). The probability of adverse response in both groups did not differ significantly (RR: 0.752 [0.412, 1.374], p > 0.05). Conclusion. Compared with sodium nitroprusside, the combined ginkgo‐damole and nitroglycerin could better control blood pressure in patients with hypertensive cerebropathy and showed enhanced clinical effects and improved safety. However, due to poor quality of the included studies, results of the present meta‐analysis should be confirmed by more stringent RCTs.
Phenolic Profile of Nipa Palm Vinegar and Evaluation of Its Antilipidemic Activities
Authors: Chatatikun Moragot , Kwanhian Wiyada
Published: September 2020

Obesity and overweight are strongly associated with dyslipidemia which can promote the development of cardiovascular diseases. Recently, natural products have been suggested as alternative compounds for antioxidant and antilipidemic activity. The objective of this study was to determine the phenolic compounds and assess the inhibitory activities on pancreatic lipase, cholesterol esterase, and cholesterol micellization of nipa palm vinegar (NPV). Total phenolic content was assessed and phenolic compounds were determined using the Folin–Ciocalteu assay and liquid chromatography‐mass spectrometry (LC‐MS), respectively. Pancreatic lipase and cholesterol esterase inhibitory activities of the NPV were measured using enzymatic colorimetric assays. The formation of cholesterol micelles was assessed using a cholesterol assay kit. The phenolic content of NPV was 167.10 ± 10.15 µg GAE/mL, and LC‐MS analyses indicated the presence of gallic acid, isoquercetin, quercetin, catechin, and rutin as bioactive compounds. Additionally, the NPV inhibited pancreatic lipase and cholesterol esterase activities in a concentration‐dependent manner. Moreover, the NPV also suppressed the formation of cholesterol micellization. These results suggest that phenolic compounds, especially gallic acid, isoquercetin, quercetin, catechin, and rutin, from NPV may be the main active compounds with possible cholesterol‐lowering effects through inhibition of pancreatic lipase and cholesterol esterase activities as well as the inhibition of solubility of cholesterol micelles. Therefore, NPV may delay postprandial dyslipidemia, and it could be used as a natural source of bioactive compounds with antilipidemic activity. However, NPV should be extensively evaluated by animal and clinical human studies.
Situation and Countermeasures of the Management Team of the Elderly Care Institutions from the Perspective of the Combination of Medical and Health Care: A Cross-Sectional Study
Authors: Yang Li , Peng Hongmei , Yang Yunfan , Ouyang Linqi , Li Yunfeng
Published: September 2020

Objective. In order to provide evidence for improving the quality of managers in elderly care institutions, this paper explored the situation of managers of elderly care institutions in a city in Central China under the national guidelines for the combination of medical and elderly health care. Design. A cross-sectional study carried out in a city in Central China was designed. Setting. The online questionnaire was distributed to the managers of six elderly care institutions in a city in Central China. Participants. The questionnaire was sent to 61 recipients; from this, 60 responses were obtained. Results. There was a 98% response rate. The study found that most managers in elderly care institutions were middle-aged, with low education level and years of management. The job mobility was high, and 27% of the managers had no relevant certificates. Management years had a significant influence on the rate of certificate holding (P<0.05). Some managers were less than 30 years old and had college degree or above, which indicated that people with young and high levels of education were more likely to become managers. However, there was no significant difference in educational level among managers of different ages (P>0.05). 56.6% of the managers have received provincial or municipal training, and few managers have received the national level training. The education level is positively related to the access to training opportunities. More than half of the managers earn less than ¥3000 a month. The study showed that the education level was positively related to the career growth space (P<0.05). Conclusions. Specialized training and high salary should be provided for managers to improve their elderly care skills and hence the quality of elderly care service. In addition, in order to improve the education level of managers, a long-term continuing education system should be established gradually. Through expanding the enrollment scale of the nursing school, carrying out training about elderly care skills, and issuing vocational skills certificates to those who pass the examination, the number of local nurses for the elderly will be increasing, and the quality of the elderly care service will be improving.
Transforaminal Interbody Impaction of Bone Graft to Treat Collapsed Nonhealed Vertebral Fractures with Endplate Destruction: A Report of Two Cases
Authors: Wegner Adam M. , Chou Yu-Hsuan , Chang Hsiao-Kang , Yin Tsung-Cheng
Published: September 2020

Background. A collapsed nonhealed vertebral fracture with endplate destruction is a challenging injury to address, as there is no single definitive treatment. We present two cases using an innovative transforaminal grafting technique to treat these patients. Case Presentation. Case 1: a 72-year-old woman had nonunion of an L1 compression fracture with destruction of both endplates. T12/L1 and L1/L2 transforaminal debridement and impaction of bone graft were performed followed by posterior instrumentation. At three years follow-up, the fusion mass between T12/L1 and L1/L2 was solid and the patient had minimal pain. Case 2: a 62-year-old woman had nonunion of an L1 burst fracture with destruction of the lower endplate. Hemilaminectomy and transforaminal interbody impaction of bone graft was performed. At three years follow-up, the patient had no back pain and a solid fusion. In both cases, local kyphosis was corrected and fusion obtained. Conclusions. Collapsed nonhealed vertebral body fractures combined with endplate destruction can be successfully treated with a one-step posterior surgery consisting of transforaminal debridement and impaction of bone graft in combination with posterior pedicle instrumentation.
Experimental Study of Slurry Flow in Mining-Induced Fractures during Longwall Overburden Grout Injection
Authors: Xuan Dayang , Li Jian , Zheng Kaidan , Xu Jialin
Published: September 2020

Slurry flow in mining-induced overburden fractures is an important theoretical concept for the grouting design of longwall overburden grout injection engineering. In this study, a visual experimental simulation system of longwall overburden grouting was designed to study the flow, pressure distribution, consolidation, and fill thickness of fly ash slurry in overburden bedding separation. Experiments showed that the slurry generates a radial and bidirectional flow during nonpressure grouting and presents itself as an approximately elliptical dominant flow channel under pressure injection. This channel expanded horizontally along the strike direction and gradually became tabular. The slurry pressure increased as the grouting time increased. Although the pressure curves at different locations exhibited similar trends, their values did not decrease as the distance from the borehole center decreased during observations. Bleeding and consolidation occurred in the slurry as soon as it flowed out of the borehole to the fracture, and the degree of consolidation increased as a function of the distance from the injection borehole. The bleeding water gathered continually to the boundary of the bedding separation fracture and was then seeped to and stored by the underlying strata based on the injection pressure. The final injection fill is manifested as a half pace with a large thickness at the center. This research provides a theoretical basis for the design and optimization of overburden grout injection in underground longwall mining.
Abstract 1037: Orally available small molecule CD73 inhibitor reverses immunosuppression through blocking of adenosine production
Authors: Du Xiaohui , Blank Brian , Chan Brenda , Chen Xi , Chen Yuping , Duong Frank , Friedman Lori , Huang Tom , Junttila Melissa R. , Kong Wayne , Metzger Todd , Moore Jared , Sun Daqing , Sun Jessica , Sutimantanapi Dena , Yuen Natalie , Zavorotinskaya Tatiana
Published: September 2020

CD73 has emerged as an attractive target for cancer immunotherapy. CD73 (ecto-5-nucleotidase) is a glycosyl phosphatidyl inositol (GPI)-anchored cell surface protein and catalyzes the hydrolysis of AMP into immunosuppressive adenosine and inorganic phosphate. CD73 is widely overexpressed in tumor microenvironments (TME) of many cancers, resulting in elevated levels of extra cellular adenosine (ADO). ADO plays a critical role in tumor progression through immune suppression, chemotherapy resistance, metastasis and angiogenesis. Therefore, reducing the level of adenosine via inhibition of CD73 has become a potential strategy for treating cancers. Here we report our medicinal chemistry efforts in developing orally available small molecule CD73 inhibitors. Based on the binding mode of adenosine 5'-(α,β-methylene)diphosphate (APCP) with CD73, we designed a novel series of monophosphate CD73 inhibitors, which are highly potent and orally bioavailable. In preclinical studies, OP-5244 inhibited ADO production completely in human cancer cells and CD8+ T cells. It also showed dose-dependent inhibitory effects on CD73 activity in various tumors ex vivo. Furthermore, OP-5244 showed PK/PD efficacy through lowering of ADO/AMP ratio and reversal of immunosuppression in vivo.

Citation Format: Xiaohui Du, Brian Blank, Brenda Chan, Xi Chen, Yuping Chen, Frank Duong, Lori Friedman, Tom Huang, Melissa R. Junttila, Wayne Kong, Todd Metzger, Jared Moore, Daqing Sun, Jessica Sun, Dena Sutimantanapi, Natalie Yuen, Tatiana Zavorotinskaya. Orally available small molecule CD73 inhibitor reverses immunosuppression through blocking of adenosine production [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1037.
Abstract 1423: A lncRNA MEG9 protects vasculature from DNA damage
Authors: Espinosa-Diez Cristina , Fraile-Bethencourt Eugenia , Hudson Clayton , Ruhl Rebecca , Anand Sudarshan
Published: September 2020

DNA damaging agents including ionizing radiation (IR) therapy are widely used in cancer patients. Previous studies have suggested that the tumor vasculature, specifically endothelial cell (ECs) dictate responses to IR. We recently showed how IR, among other DNA damaging agents, induced changes in microRNA programs and impacted tumor angiogenesis. Here, we describe how different DNA damaging agents affect long noncoding RNA (lncRNA) programs in vascular cells. Specifically, we identify lncRNA MEG9 (Maternally Expressed Gene 9 in humans, Mirg in mouse) as one of the most differentially expressed lncRNAs in angiogenic stimuli and stress responses. MEG9 is robustly induced by DNA damaging agents and suppressed by vascular growth factors. MEG9 is located in the DLK1-DIO3 imprinted cluster. Previous studies have shown how DLK1-DIO3 genes are associated with stem cell biology and with the pathogenesis of several diseases, such as cancer. Other studies have shown that microRNAs in this cluster are regulated by methylation. Consistent with this observation, we found that inhibition of DNA methylation either via 5-azacytidine or silencing of DNMT3b significantly upregulated de novo expression of MEG9. Gain and loss of function assays indicated an anti-apoptotic role of MEG9 via caspase 3/7 pathways in cultured ECs. Similarly, MEG9 inhibition decreased angiogenesis in a 3D sprouting angiogenesis assay. Interestingly, MEG9 inhibition in ECs accelerated fibrin formation suggesting a regulatory role for this lncRNA in thrombosis. Moreover, we observed that MEG9 inhibition affects vascular permeability in vitro and in vivo in bFGF-Matrigel plugs. Finally, systemic delivery of RNAi targeting Mirg (mouse MEG9) decreased tumor burden in a mouse model of triple negative mammary carcinoma. Our mechanistic studies indicated that MEG9 in ECs impacts pathways related to inflammation and thrombosis, both critical mediators of tumor responses to radiation. Taken together, our results show MEG9 as a novel DNA damage induced lncRNA with a protective role in the tumor vasculature functioning via multiple distinct mechanisms. Therefore, we propose that disruption of lncRNA MEG9 is a potent anti-angiogenic strategy that can synergize with DNA damaging agents.

Citation Format: Cristina Espinosa-Diez, Eugenia Fraile-Bethencourt, Clayton Hudson, Rebecca Ruhl, Sudarshan Anand. A lncRNA MEG9 protects vasculature from DNA damage [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1423.
Abstract 1698: Cellular cytotoxicity is a form of immunogenic cell death
Authors: Minute Luna , Teijeira Alvaro , Sánchez-Paulete Alfonso Rodriguez , del Carmen Ochoa Maria , Alvarez Maite , Otano Itziar , Etxeberria Iñaki , Bolaños Elixabet , Azpilikueta Arantza , Garasa Saray , Casares Noelia , Pérez-Gracia José Luiz , Rodríguez-Ruiz Maria Esperanza , Berraondo Pedro , Melero Ignacio
Published: September 2020

Background: The immune response to cancer is often conceptualized with the Cancer Immunity Cycle. An essential step in this interpretation is that antigens released by dying tumors are presented by dendritic cells to naive or memory T cells in the tumor-draining lymph nodes. Whether tumor cell death resulting from cytotoxicity, as mediated by T cells or NK lymphocytes, is actually immunogenic currently remains unknown.

Methods: In this study, tumor cells were killed by antigen-specific T-cell receptor (TCR) transgenic CD8 T cells or activated natural killer cells. Immunogenic cell death was studied analyzing the membrane exposure of calreticulin and the release of high mobility group box 1 (HMGB1) by the dying tumor cells. Furthermore, the potential immunogenicity of the tumor cell debris was evaluated in immunocompetent mice challenged with an unrelated tumor sharing only one tumor-associated antigen and by class I MHC-multimer stainings. Mice deficient in BATF-3, IFNAR and STING were used to study mechanistic requirements.

Results: We observe in co-cultures of tumor cells and effector cytotoxic cells, the presence of markers of immunogenic cell death such as calreticulin exposure and soluble HMGB1 protein. OVA-transfected MC38 colon cancer cells, exogenously pulsed to present the gp100 epitope are killed in culture by mouse gp100 specific TCR transgenic CD8 T cells. Immunization of mice with the resulting destroyed cells induces epitope spreading as observed by detection of OVA-specific T cells by MHC multimer staining and rejection of OVA+ EG7 lymphoma cells. Similar results were observed in mice immunized with cell debris generated by NK-cell mediated cytotoxicity. Mice deficient in BATF3-dependent dendritic cells (cDC1) fail to develop an anti-OVA response when immunized with tumor cells killed by cytotoxic lymphocytes. In line with this, cultured cDC1 dendritic cells uptake and can readily cross-present antigen from cytotoxicity-killed tumor cells to cognate CD8+ T lymphocytes.

Conclusion: These results support that an ongoing cytotoxic antitumor immune response can lead to immunogenic tumor cell death.

Citation Format: Luna Minute, Alvaro Teijeira, Alfonso Rodriguez Sánchez-Paulete, Maria del Carmen Ochoa, Maite Alvarez, Itziar Otano, Iñaki Etxeberria, Elixabet Bolaños, Arantza Azpilikueta, Saray Garasa, Noelia Casares, José Luiz Pérez-Gracia, Maria Esperanza Rodríguez-Ruiz, Pedro Berraondo, Ignacio Melero. Cellular cytotoxicity is a form of immunogenic cell death [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1698.