bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Syngas Addition to Methane on Laminar Burning Velocity
Authors: Morovatiyan Mohammadrasool , Shahsavan Martia , Baghirzade Mammadbaghir , Mack J. Hunter
Published: November 2020

Exhaust gas recirculation (EGR) in spark-ignited (SI) engines is a key technique to reduce in-cylinder NOx production by decreasing the combustion temperature. The major species of the exhaust gas in rich combustion of natural gas are hydrogen and carbon monoxide, which can subsequently be recirculated to the cylinders using EGR. In this study, the effect of hydrogen and carbon monoxide addition to methane on laminar burning velocity and flame morphology is investigated. Due to the broad flammability limit and high burning velocity of hydrogen compared to methane, this addition to the gaseous mixture leads to an increase in burning velocity, less emissions production, and a boost to the thermal efficiency of internal combustion engines. Premixed CH4–H2–CO–air flames are experimentally investigated using an optically accessible constant volume combustion chamber (CVCC) accompanied with a high-speed Z-type Schlieren imaging system. Furthermore, a numerical code is applied to quantify the laminar burning velocity based on the pressure rise during flame propagation within the CVCC. According to the empirical and numerical results, the addition of hydrogen and carbon monoxide enhances laminar burning velocity while influencing the flame structure and development.
Time-Domain Adaptive Higher Harmonic Control for Rejection of Sinusoidal Disturbances
Authors: Kamaldar Mohammadreza , Hoagg Jesse B.
Published: November 2020

This paper presents two new time-domain feedback controllers that reject sinusoidal disturbances with known frequencies acting on an asymptotically stable linear time-invariant (LTI) system. The first controller is time-domain higher harmonic control (TD-HHC), which is effective for uncertain LTI systems. The second controller is time-domain adaptive higher harmonic control (TD-AHHC), which is effective for completely unknown LTI systems. TD-HHC requires an estimate of the control-to-performance transfer function evaluated at the disturbance frequencies. In contrast, TD-AHHC does not require any information regarding the LTI system. We analyze the stability and closed-loop performance of TD-HHC and TD-AHHC. For both TD-HHC and TD-AHHC, we show that the controller asymptotically rejects the disturbance. We present numerical simulations comparing TD-HHC and TD-AHHC with frequency-domain higher harmonic control (FD-HHC), which is an existing frequency-domain controller for rejection of sinusoidal disturbances. We also present results from acoustic disturbance rejection experiments, which demonstrate the practical effectiveness of both TD-HHC and TD-AHHC.
In Vivo Experimental and Analytical Studies for Bevacizumab Diffusion Coefficient Measurement in the Rabbit Vitreous Humor
Authors: Zhang Shuqi , Penkova Anita , Humayun Mark S. , Martinez-Camarillo Juan Carlos , Tadle Abegail C. , Galesic Ana , Thompson Mark E. , Pratt Matthew , Gonzales-Calle Alejandra , Sadhal Satwindar Singh
Published: November 2020

In order to measure the effective diffusion coefficient D of Bevacizumab (Avastin, Genentech) in the vitreous humor, a new technique is developed based on the “contour method” and in vivo optical coherence tomography measurements. After injection of Bevacizumab-fluorescein conjugated compound solution into the rabbit eye, the contours of drug concentration distribution at the subsurface of injection were tracked over time. The 2D contours were extrapolated to 3D contours using reasonable assumptions and a numerically integrated analytical model was developed for the theoretical contours for the irregularly shaped drug distribution in the experimental result. By floating the diffusion coefficient, different theoretical contours were constructed and the least-squares best fit to the experimental contours was performed at each time point to get the best fit solution. The approach generated consistent diffusion coefficient values based on the experiments on four rabbit eyes over a period of 3 h each, which gave D=1.2±0.6×10−6 cm2/s, and the corresponding theoretical contours matched well with the experimental contours. The quantitative measurement of concentration using optical coherence tomography and fluorescein labeling gives a new approach for the “noncontact” in vivo drug distribution measurement within vitreous.
Numerical Development of a Coupled One-Dimensional/Three-Dimensional Computational Fluid Dynamics Method for Thermal Analysis With Flow Maldistribution
Authors: Jordaan Haimi , Stephan Heyns P. , Hoseinzadeh Siamak
Published: November 2020

This work describes the development of a methodology that couples one-dimensional (1D) network elements with three-dimensional spatial computational fluid dynamic (CFD) elements to analyze shell-and-tube heat exchangers with dense tube bundles. The 1D elements represent the tube flow while the spatial elements represent the external auxiliary flow. This reduces the computational expense significantly as compared to full computational fluid dynamics analysis of the same system, while a detailed transient temperature distribution can still be obtained. The methodology uses a unique combination of relaxation algorithms, a polynomial regression mapping procedure, and discretisation methods to create a coherent numerical methodology. Simulations are performed on a TEMA-FU-type shell-and-tube heat exchanger. The methodology was validated against full CFD and indicates errors between the calculated logarithmic mean temperature differences (LMTD) of less than 2% over a range of turbulent flow conditions. Various combinations of media for primary and auxiliary fluids are considered, to test the applicability and robustness of the methodology. Finally, a transient simulation of timed step inputs for the flowrate and temperature of both primary and auxiliary fluids also corresponds with a full CFD analysis. It is concluded that the proposed 1D-CFD method is effective for simplifying the analysis of flow-through tube bundles.
Investigation of Nanofluids Circulating in a Volumetric Solar Receiver
Authors: Zanetti Emanuele , Dugaria Simone , Biscaglia Francesca , Agresti Filippo , Fedele Laura , Meneghetti Moreno , Del Col Davide
Published: November 2020

Single-wall carbon nanohorn (SWCNHs)-based nanofluids have been proven to be promising media for the direct absorption of solar radiation due to their favorable optical properties and potential low cost. Still their stability in real working conditions is an open issue because they have been studied mainly under stagnant conditions, while limited information is available on the performance of these nanofluids during circulation in real systems. In the present work, the optical behavior of SWCNH-based nanofluids has been investigated with the aim of detecting possible effects of circulation and exposure to radiation, avoiding other effects such as thermal instability. An ad hoc experimental apparatus has been realized to check the stability of the circulating fluids in situ using a novel approach based on the use of pyranometers. Three suspensions are tested, two are surfactant stabilized and one is based on preoxidized and functionalized SWCNHs. Efficiency values higher than 90% were measured for more than 65 h of circulation. The effects of fluid circulation and exposure to solar radiation have been addressed, finding that the absorption efficiency decreases during tests due to the degradation of the optical properties and the nanofluid circulation is the main responsible for such degradation.
Discussing surgical innovation with patients: a qualitative study of surgeons’ and governance representatives’ views
Authors: Zahra Jesmond , Paramasivan Sangeetha , Blencowe Natalie S , Cousins Sian , Avery Kerry , Mathews Johnny , Main Barry G , McNair Angus G K , Hinchliffe Robert , Blazeby Jane M , Elliott Daisy
Published: November 2020

Objectives

Little is known about how innovative surgical procedures are introduced and discussed with patients. This qualitative study aimed to explore perspectives on information provision and consent prior to innovative surgical procedures.

Design

Qualitative study involving semi-structured interviews. Interviews were audio recorded, transcribed and analysed thematically.

Participants

42 interviews were conducted (26 surgeons and 16 governance representatives).

Setting

Surgeons and governance representatives recruited from various surgical specialties and National Health Service (NHS) Trusts across England, UK.

Results

Participants stated that if a procedure was innovative, patients should be provided with additional information extending beyond that given during routine surgical consultations. However, difficulty defining innovation had implications for whether patients were informed about novel components of surgery and how the procedure was introduced (ie, as part of a research study, trust approval or in routine clinical practice). Furthermore, data suggest surgeons found it difficult to establish what information is essential and how much detail is sufficient, and governance surrounding written and verbal information provision differed between NHS Trusts. Generally, surgeons believed patients held a view that ‘new’ was best and reported that managing these expectations could be difficult, particularly if patient views aligned with their own.

Conclusions

This study highlights the challenges of information provision and obtaining informed consent in the context of innovative surgery, including establishing if and how a procedure is truly innovative, determining the key information to discuss with patients, ensuring information provision is objective and balanced, and managing patient expectations and preferences. This suggests that surgeons may require support and training to discuss novel procedures with patients. Further work should capture consultations where new procedures are discussed with patients and patients’ views of these information exchanges.
Demographic and socioeconomic patterns in healthcare-seeking behaviour for respiratory symptoms in England: a comparison with non-respiratory symptoms and between three healthcare services
Authors: Morrison Kirsty E , Colón-González Felipe J , Morbey Roger A , Hunter Paul R , Rutter Judith , Stuttard Gareth , de Lusignan Simon , Yeates Alex , Pebody Richard , Smith Gillian , Elliot Alex J , Lake Iain R
Published: November 2020

Objective

This study will analyse respiratory contacts to three healthcare services that capture more of the community disease burden than acute data sources, such as hospitalisations. The objective is to explore associations between contacts to these services and the patient’s age, gender and deprivation. Results will be compared between healthcare services, and with non-respiratory contacts to explore how contacts differ by service and illness. It is crucial to investigate the sociodemographic patterns in healthcare-seeking behaviour to enable targeted public health interventions.

Design

Ecological study.

Setting

Surveillance of respiratory contacts to three healthcare services in England: telehealth helpline (NHS111); general practitioner in-hours (GPIH); and general practitioner out of hours unscheduled care (GPOOH).

Participants

13 million respiratory contacts to NHS111, GPIH and GPOOH.

Outcome measures

Respiratory contacts to NHS111, GPIH and GPOOH, and non-respiratory contacts to NHS111 and GPOOH.

Results

More respiratory contacts were observed for females, with 1.59, 1.73, and 1.95 times the rate of contacts to NHS111, GPOOH and GPIH, respectively. When compared with 15–44 year olds, there were 37.32, 18.66 and 6.21 times the rate of respiratory contacts to NHS111, GPOOH and GPIH in children <1 year. There were 1.75 and 2.70 times the rate of respiratory contacts in the most deprived areas compared with the least deprived to NHS111 and GPOOH. Elevated respiratory contacts were observed for males <5 years compared with females <5 years. Healthcare-seeking behaviours between respiratory and non-respiratory contacts were similar.

Conclusion

When contacts to services that capture more of the disease burden are explored, the demographic patterns are similar to those described in the literature for acute systems. Comparable results were observed between respiratory and non-respiratory contacts suggesting that when a wider spectrum of disease is explored, sociodemographic factors may be the strongest influencers of healthcare-seeking behaviour.
Added value of assessing medical students’ reflective writings in communication skills training: a longitudinal study in four academic centres
Authors: Ament Giuliani Franco Camila , Franco Renato Soleiman , Cecilio-Fernandes Dario , Severo Milton , Ferreira Maria Amélia , de Carvalho-Filho Marco Antonio
Published: November 2020

Objectives

This study describes the development and implementation of a model to assess students’ communication skills highlighting the use of reflective writing. We aimed to evaluate the usefulness of the students’ reflections in the assessment of communication skills.

Design

Third-year and fourth-year medical students enrolled in an elective course on clinical communication skills development were assessed using different assessment methods.

Setting and participants

The communication skills course was offered at four universities (three in Brazil and one in Portugal) and included 69 students.

Outcome measures

The students were assessed by a Multiple-Choice Questionnaire (MCQ), an objective structured clinical examination (OSCE) and reflective writing narratives. The Cronbach’s alpha, dimensionality and the person’s correlation were applied to evaluate the reliability of the assessment methods and their correlations. Reflective witting was assessed by applying the Reflection Evaluation for Enhanced Competencies Tool Rubric (Reflect Score (RS)) to measure reflections’ depth, and the Thematic Score (TS) to map and grade reflections’ themes.

Results

The Cronbach alpha for the MCQ, OSCE global score, TS and RS were, respectively, 0.697, 0.633, 0.784 and 0.850. The interobserver correlation for the TS and RS were, respectively, 0.907 and 0.816. The assessment of reflection using the TS was significantly correlated with the MCQ (r=0.412; p=0.019), OSCE (0.439; p=0.012) and RS (0.410; p=0.020). The RS did not correlate with the MCQ and OSCE.

Conclusions

Assessing reflection through mapping the themes and analysing the depth of reflective writing expands the assessment of communication skills. While the assessment of reflective themes is related to the cognitive and behavioural domains of learning, the reflective depth seems to be a specific competence, not correlated with other assessment methods—possibly a metacognitive domain.
Pharmaceutical management of elderly high-risk patients in perioperative settings (PHAROS): protocol of a pilot sequential intervention study
Authors: Richter Julia , Schönfeld Moritz Sebastian , Langebrake Claudia , Bergelt Corinna , Kriston Levente , Olotu Cynthia , Kiefmann Rainer
Published: November 2020

Introduction

With increasing age, the risk of complications after surgery rises in elderly patients. Furthermore, the prevalence of multimorbidity and polypharmacy rises with age, making this elderly population especially vulnerable for drug-related problems and posing an additional risk for postoperative complications. Still, only few studies have concentrated on investigating how medication safety can be improved in these patients. The aim of this pilot study is to examine the impact of a comprehensive intervention (interprofessional systematic medication therapy management) on medication appropriateness in elderly polymedicated, multimorbid patients during hospital stay for elective surgery.

Methods and analysis

This pilot study will include a total number of 140 patients. Surgical high-risk patients ≥65 years taking more than five chronic systemic drugs will be recruited consecutively for 9 months in the control group capturing usual care regarding medication history and in-hospital medication therapy management without any study intervention. Recruitment of the intervention group will be conducted for another 9 months. The intervention consists of the following components: an additional medication history by a hospital pharmacist before admission, a subsequent medication review, optimisation of the long-term medication and recommendations to the patient’s general practitioner. A follow-up will be performed 3 months after surgery. As the primary study outcome, medication appropriateness will be measured using the Medication Appropriateness Index.

Secondary outcomes are postoperative complications, incidence and frequency of adverse drug reactions and potentially inappropriate medication in the elderly, satisfaction with inpatient and outpatient care, medication reconciliation and health-related quality of life. Multivariable analyses will be used to analyse all quantitative research questions.

Ethics and dissemination

Ethics approval was obtained by the medical ethics committee of the Medical Chamber of Hamburg (study ID: PV5754). Data will be published in peer-reviewed journals and presented at conferences.

Trial registration number

The study is registered at www.drks.de: DRKS00014621.
Safe clinical practice for patients hospitalised in mental health wards during a suicidal crisis: qualitative study of patient experiences
Authors: Berg Siv Hilde , Rørtveit Kristine , Walby Fredrik A. , Aase Karina
Published: November 2020

Aim

The aim of this study was to explore suicidal patients’ experiences of safe clinical practice during hospitalisation in mental health wards. The study was guided by the following research question: How do suicidal patients experience safe clinical practice during hospitalisation in mental health wards?

Design, setting and participants

A qualitative design with semistructured individual interviews was applied. Eighteen patients hospitalised with suicidal behaviour in specialised mental health wards for adults at a Norwegian hospital participated in the study. Data were analysed thematically and inductively using qualitative content analysis.

Results

Patients in a suicidal crisis experienced safe clinical care in mental health wards characterised by the following three themes: (1) being recognised as suicidal, (2) receiving tailor-made treatment and (3) being protected by adaptive practice.

Conclusion

This study illuminates the experiences of safe clinical practice for patients in a suicidal crisis. The patient group was multifaceted, with variable experiences of how safe clinical practice affected their subjective experience of safety and suicidal behaviour. The finding highlights the importance of embracing personalised activities in all parts of safe clinical practice and to recognise rather than efface patients’ variability in patient safety efforts.
Transformation of the Tanzania medical store department through global fund support: an impact assessment study
Authors: Githendu Patrick , Morrison Linden , Silaa Rosemary , Pothapregada Sai , Asiimwe Sarah , Idris Rafiu , Peterson Tatjana , Davidson Emma , Lesego Abaleng , Mwale Neema , Mwakalobo Sako Mayrick , Bwanakunu Laurean Rugambwa , Achoki Tom
Published: November 2020

Background

The Tanzania government sought support from The Global Fund to Fight AIDs, Tuberculosis and Malaria to reform its Medical Stores Department, with the aim of improving performance. The study sought to assess the impact of the reforms and document the lessons learnt.

Methods

Quantitative and qualitative research methods were applied to assess the impact of the reforms. The quantitative part entailed a review of operational and financial data covering the period before and after the implementation of the reforms. Interrupted time series analysis was used to determine the change in average availability of essential health commodities at health zones. Qualitative data were collected through 41 key informant interviews. Participants were identified through stakeholder mapping, purposive and snowballing sampling techniques and responses were analysed through thematic content analysis.

Results

Availability of essential health commodities increased significantly by 12.6% (95% CI 9.6% to 15.6%) after the reforms and continued to increase on a monthly basis by 0.2% (95%CI 0.0% to 0.3%) relative to the preintervention trend. Sales increased by 56.6% while the cost of goods sold increased by 88.6% between 2014/2015 and 2017/2018. Surplus income increased by 56.4% between 2014/2015 and 2017/2018 with reductions in rent and fuel expenditure. There was consensus among study participants that the reforms were instrumental in improving performance of the Medical Stores Department.

Conclusion

Positive results were realised through the reforms. However, despite the progress, there were risks such as the increasing government receivable that could jeopardise the sustainability of the gains. Therefore, multistakeholder efforts are necessary to make progress and expand public health.
Abdominal aortic aneurysm is associated with subarachnoid hemorrhage
Authors: Wilkinson D Andrew , Daou Badih J , Nadel Jeffrey L , Chaudhary Neeraj , Gemmete Joseph J , Thompson Byron Gregory , Pandey Aditya S
Published: November 2020

Background

Although intracranial aneurysms (IA) and abdominal aortic aneurysms (AAA) share similar risk factors, little is known about the relationship between them. Previous studies have shown an increased incidence of IA in patients with AAA, though the rate of subarachnoid hemorrhage (SAH) in patients with AAA has not been described.

Objective

To use claims data with longitudinal follow-up, to evaluate the incidence of aneurysmal SAH in patients diagnosed with AAA.

Methods

We examined longitudinally linked medical claims data from a large private insurer to determine rates of aneurysmal SAH (aSAH) and secured aSAH (saSAH) in 2004–2014 among patients with previously diagnosed AAA.

Results

We identified 62 910 patients diagnosed with AAA and compared them 5:1 with age- and sex-matched controls. Both populations were predominantly male (70.9%), with an average age of 70.8 years. Rates of hypertension (69.7% vs 50.6%) and smoking (12.8% vs 4.1%) were higher in the AAA group (p<0.0001) than in controls. Fifty admissions for aSAH were identified in patients with AAA (26/100 000 patient-years, 95% CI 19 to 44) and 115 admissions for aSAH in controls (7/100 000 years, 95% CI 6 to 9), giving an incidence rate ratio (IRR) of 3.6 (95% CI 2.6 to 5.0, p<0.0001) and a comorbidity-adjusted incidence rate ratio (IRR) of 2.8 (95% CI 1.9 to 3.9) for patients with AAA. The incidence of secured aneurysmal SAH was proportionally even higher in patients with AAA, 7 vs 2/100 000 years, IRR 4.5 (95% CI 3.2 to 6.3, p<0.0001).

Conclusion

SAH rate was elevated in patients with AAA, even after adjustment for comorbidities. Among risk factors evaluated, AAA was the strongest predictor for SAH. The relative contributions of common genetic and environmental risk factors to both diseases should be investigated.
Performance of Radiomics derived morphological features for prediction of aneurysm rupture status
Authors: Ludwig Calvin Gerald , Lauric Alexandra , Malek Justin A , Mulligan Ryan , Malek Adel M
Published: November 2020

Background

Morphological differences between ruptured and unruptured cerebral aneurysms represent a focus of neuroimaging researchfor understanding the mechanisms of aneurysmal rupture. We evaluated the performance of Radiomics derived morphological features, recently proposed for rupture status classification, against automatically measured shape and size features previously established in the literature.

Methods

353 aneurysms (123 ruptured) from three-dimensional rotational catheter angiography (3DRA) datasets were analyzed. Based on a literature review, 13 Radiomics and 13 established morphological descriptors were automatically extracted per aneurysm, and evaluated for rupture status prediction using univariate and multivariate statistical analysis, yielding an area under the curve (AUC) metric of the receiver operating characteristic.

Results

Validation of overlapping descriptors for size/volume using both methods were highly correlated (p<0.0001,R2=0.99). Univariate analysis selected AspectRatio (p<0.0001, AUC=0.75), Non-sphericity Index (p<0.0001, AUC=0.75), Height/Width (p<0.0001, AUC=0.73), and SizeRatio (p<0.0001, AUC=0.73) as best among established descriptors, and Elongation (p<0.0001, AUC=0.71) and Flatness (p<0.0001, AUC=0.72) among Radiomics features. Radiomics Elongation correlated best with established Height/Width (R2=0.52), whereas Radiomics Flatness correlated best with Ellipticity Index (R2=0.54). Radiomics Sphericity correlated best with Undulation Index (R2=0.65). Best Radiomics performers, Elongation and Flatness, were highly correlated descriptors (p<0.0001,R2=0.75). In multivariate analysis, established descriptors (Height/Width, SizeRatio, Ellipticity Index; AUC=0.79) outperformed Radiomics features (Elongation, Maximum3Ddiameter; AUC=0.75).

Conclusion

Although recently introduced Radiomics analysis for aneurysm shape and size evaluation has the advantage of being an efficient operator independent methodology, it currently offers inferior rupture status discriminant performance compared with established descriptors. Future research is needed to extend the current Radiomics feature set to better capture aneurysm shape information.
Approximate analytical solution for ionizing cylindrical shock wave in rotational axisymmetric non-ideal gas: isothermal flow
Authors: Nath G. , Singh Sumeeta
Published: November 2020

The propagation of an ionizing cylindrical shock wave in rotational axisymmetric non-ideal gas under isothermal flow condition with an azimuthal magnetic field is investigated. The electrical conductivity is assumed to be negligible in the medium ahead of the shock wave, which after the passage of the shock wave becomes infinitely large. The magnetic pressure, azimuthal fluid velocity, and axial fluid velocity are assumed to be varying according to the power law with distance from the axis of symmetry in the undisturbed medium. The zeroth and first-order approximations are discussed by the aid of the power series method. Solutions for the zeroth-order approximation are constructed in analytical form. Distributions of hydrodynamical quantities are discussed. The effect of flow parameters, namely, shock wave Cowling number c∗, adiabatic exponent γ, rotational parameter L, and gas non-idealness parameter [Formula: see text] are studied on the flow variables. Due to the consideration of a rotating medium or due to the presence of magnetic field, the total energy of the disturbance increases, while with an increase in adiabatic exponent γ the total energy of the disturbance decreases. Density and pressure vanish near the axis of symmetry, thus forming a vacuum there.
Quark and pion condensates at finite isospin density in chiral perturbation theory
Authors: Adhikari Prabal , Andersen Jens O.
Published: November 2020

In this paper, we consider two-flavor QCD at zero temperature and finite isospin chemical potential $$\mu _I$$

μ
I

using a model-independent analysis within chiral perturbation theory at next-to-leading order. We calculate the effective potential, the chiral condensate and the pion condensate in the pion-condensed phase at both zero and nonzero pionic source. We compare our finite pionic source results for the chiral condensate and the pion condensate with recent (2+1)-flavor lattice QCD results. Agreement with lattice results generally improves as one goes from leading order to next-to-leading order.
Pandemic Pulse
Authors: Krieg Steven J. , Schnur Jennifer J. , Marshall Jermaine D. , Schoenbauer Matthew M. , Chawla Nitesh V.
Published: November 2020

COVID-19 has presented society with a unique set of challenges, including seeking a scientific understanding of the novel coronavirus, modeling its epidemiology, and inferring appropriate societal response. In this article, we posit that fighting a pandemic is as much a social endeavor as a medicinal and scientific one and focus on developing a platform for understand the social pulse of the United States during the COVID-19 crisis. We collected a multitude of data that includes longitudinal trends of news topics, social distancing behaviors, community mobility changes, web searches, and other descriptors of the COVID-19 pandemic’s effects on the United States. Our preliminary results show that the number of COVID-19-related news articles published immediately after the World Health Organization declared the pandemic on March 11 have steadily decreased—regardless of changes in the number of cases or public policies. Additionally, we found that politically moderate and scientifically grounded sources have, relative to baselines measured before the beginning of the pandemic, published a lower proportion of COVID-19 news articles than more politically extreme sources—a fact that has implications for the spread and consequences of misinformation during the pandemic. We suggest that further analysis of these multi-modal signals could produce meaningful social insights and present an interactive dashboard to aid further exploration.
1
Numerical Test Research on Loading Rate Effect of Rock Mass with Transfixion Sawtooth Structural Plane
Authors: Li Dongsong , Du Yanhong , Chen Feng , Ma Tianhui
Published: November 2020

In this paper, numerical test research is carried out on the loading rate effect of a numerical specimen (sample C) with a transfixion sawtooth structural plane by using the rock failure process analysis (RFPA) 2D software. In order to study the mechanical characteristics difference between the rock mass with this kind of structural plane and other rock masses, the intact numerical specimen (sample A) of no structural plane and the numerical specimen (sample B) with smooth structural plane are also simulated. The uniaxial compression tests were carried out for each specimen under five loading rates of 0.002, 0.005, 0.008, 0.02, and 0.05 mm/s. The following several conclusions are obtained by the numerical test. When the loading rate is 0.002 or 0.005 mm/s, the failure mode of the numerical specimen C is an inclined linear fracture zone located in the middle and lower part of the rock mass; however, when the loading rate rises to 0.008, 0.02, and 0.05 mm/s, the fracture zone of the numerical specimen C is located in the middle and upper part of the rock mass, and its inclination angle is about 60 degrees. The peak strength, residual strength, and stress drop of the specimens A, B, and C increase with the addition of loading rate; the peak strength and stress drop of the sample C are higher than those of the other two samples. When the loading rate is 0.002 mm/s, the residual strength of sample C is lower than that of samples A and B, and the other four kinds of loading conditions are higher than those of specimens A and B. Based on the acoustic emission (AE) information, it can be seen that the failure modes of the numerical specimen C under five loading conditions are tensile failure. The AE accumulated energy decreases with the increase of loading rate, but the change law of AE accumulated number is opposite.
Analysis of Some Heavy Metals and Organic Acids in Ficus carica Growing Adjacent in the Serpentine Soil in Sulaimani/Kurdistan, Iraq
Authors: Mohammed Othman Abdulrahman , Hussain Mohammed Rawf , Shareef Osama Hamid , Hama Abdullah Ahmed , Weli Sardar Mohammed , Ali Fatimah Mohammed , Salih Sabiha Sharif
Published: November 2020

Serpentine soil refers to soil having magnesium-rich minerals such as chrysotile, lizardite, and antigorite. Fig (Ficus carica) is a plant of major importance in the world. It is a nourishing food and is used in industrial productions. This study analyzes the distribution of heavy metal contents such as nickel, cobalt, zinc, and manganese in different parts of this plant, such as its leaves, stems, and fruits. Furthermore, the organic acid content, including citric acid, fumaric acid, malic acid, and oxalic acid, was estimated. The studied area is known as Kunjirin which is a village located in the northwestern extension of the Zagros-fold-thrust belt in Mawat town, northeast of Sulaimani Province, Kurdistan Region of Iraq. The results show that there are significant differences in heavy metal contents among the plant organs except for zinc. The lowest level of heavy metals is in the fruits, while the highest amount of the heavy metal content is in the leaves. Moreover, the organic acids were unequally distributed in the plant organs. However, the lowest level of organic acids are found in the stem, while the highest concentration of the organic acids are found in the fruit part of the plant. The present study concludes that the level of heavy metals in the fruit part is within the legally admitted limits. This indicates that it is normal for human beings and animals to consume such fruits.
AEBP1 Promotes Glioblastoma Progression and Activates the Classical NF-κB Pathway
Authors: Guo Kai , Song Lei , Chang Jianyong , Cao Peicheng , Liu Qi
Published: November 2020

Objective. Our study was aimed at investigating the mechanistic consequences of the upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in glioblastoma (GBM). Methods. The expression of AEBP1 in GBM was assessed by bioinformatics analysis and qRT-PCR; the effects of AEBP1 on GBM cell proliferation, migration, invasion, and tumor growth in vitro and in vivo were detected by a CCK-8 assay, colony formation assay, scratch assay, Transwell assay, and subcutaneous tumor formation, respectively. The activation of related signaling pathways was monitored using western blot. Results. Tumor-related databases and bioinformatics analysis revealed that AEBP1 was highly expressed in GBM and indicated poor outcome of patients; its high expression that was also confirmed in GBM tissues and cell lines was closely related to the tumor size. The results of in vitro experiments showed that AEBP1 could significantly promote GBM cell proliferation, migration, and invasion; in vivo experiments suggested that AEBP1 could contribute to the growth of GBM tumors. AEBP1 could upregulate the level of IκBα phosphorylation, decrease IκBα expression, activate the NF-κB signaling pathway, and promote the expression of downstream oncogenes. Conclusion. Upregulated AEBP1 in GBM promotes GBM cell proliferation, migration, and invasion and facilitates tumor growth in vivo by activating the classical NF-κB pathway.
New Estimates for Csiszár Divergence and Zipf–Mandelbrot Entropy via Jensen–Mercer’s Inequality
Authors: Adil Khan Muhammad , Husain Zakir , Chu Yu-Ming
Published: November 2020

Jensen’s inequality is one of the fundamental inequalities which has several applications in almost every field of science. In 2003, Mercer gave a variant of Jensen’s inequality which is known as Jensen–Mercer’s inequality. The purpose of this article is to propose new bounds for Csiszár and related divergences by means of Jensen–Mercer’s inequality. Also, we investigate several new bounds for Zipf–Mandelbrot entropy. The idea of this article may further stimulate research on information theory with the help of Jensen–Mercer’s inequality.
Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer
Authors: Wan Changxin , Keany Matthew P. , Dong Han , Al-Alem Linah F. , Pandya Unnati M. , Lazo Suzan , Boehnke Karsten , Lynch Katherine N. , Xu Rui , Zarrella Dominique T. , Gu Shengqing , Cejas Paloma , Lim Klothilda , Long Henry W. , Elias Kevin M. , Horowitz Neil S. , Feltmate Colleen M. , Muto Michael G. , Worley Michael J. , Berkowitz Ross S. , Matulonis Ursula A. , Nucci Marisa R. , Crum Christopher P. , Rueda Bo R. , Brown Myles , Liu Xiaole Shirley , Hill Sarah J.
Published: November 2020

Immune therapies have had limited efficacy in high-grade serous ovarian cancer (HGSC), as the cellular targets and mechanism(s) of action of these agents in HGSC are unknown. Here we performed immune functional and single-cell RNA sequencing transcriptional profiling on novel HGSC organoid/immune cell co-cultures treated with a unique bispecific anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibody compared with monospecific anti-PD-1 or anti-PD-L1 controls. Comparing the functions of these agents across all immune cell types in real time identified key immune checkpoint blockade (ICB) targets that have eluded currently available monospecific therapies. The bispecific antibody induced superior cellular state changes in both T and natural killer (NK) cells. It uniquely induced NK cells to transition from inert to more active and cytotoxic phenotypes, implicating NK cells as a key missing component of the current ICB-induced immune response in HGSC. It also induced a subset of CD8 T cells to transition from naïve to more active and cytotoxic progenitor-exhausted phenotypes post-treatment, revealing the small, previously uncharacterized population of CD8 T cells responding to ICB in HGSC. These state changes were driven partially through bispecific antibody-induced downregulation of the bromodomain-containing protein BRD1. Small-molecule inhibition of BRD1 induced similar state changes in vitro and demonstrated efficacy in vivo, validating the co-culture results. Our results demonstrate that state changes in both NK and a subset of T cells may be critical in inducing an effective anti-tumor immune response and suggest that immune therapies able to induce such cellular state changes, such as BRD1 inhibitors, may have increased efficacy in HGSC.

Significance:

This study indicates that increased efficacy of immune therapies in ovarian cancer is driven by state changes of NK and small subsets of CD8 T cells into active and cytotoxic states.
A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer
Authors: Somarelli Jason A. , Roghani Roham Salman , Moghaddam Ali Sanjari , Thomas Beatrice C. , Rupprecht Gabrielle , Ware Kathryn E. , Altunel Erdem , Mantyh John B. , Kim So Young , McCall Shannon J. , Shen Xiling , Mantyh Christopher R. , Hsu David S.
Published: November 2020

Colorectal cancer is the third most common cancer in the United States and responsible for over 50,000 deaths each year. Therapeutic options for advanced colorectal cancer are limited, and there remains an unmet clinical need to identify new treatments for this deadly disease. To address this need, we developed a precision medicine pipeline that integrates high-throughput chemical screens with matched patient-derived cell lines and patient-derived xenografts (PDX) to identify new treatments for colorectal cancer. High-throughput screens of 2,100 compounds were performed across six low-passage, patient-derived colorectal cancer cell lines. These screens identified the CDK inhibitor drug class among the most effective cytotoxic compounds across six colorectal cancer lines. Among this class, combined targeting of CDK1, 2, and 9 was the most effective, with IC50s ranging from 110 nmol/L to 1.2 μmol/L. Knockdown of CDK9 in the presence of a CDK2 inhibitor (CVT-313) showed that CDK9 knockdown acted synergistically with CDK2 inhibition. Mechanistically, dual CDK2/9 inhibition induced significant G2–M arrest and anaphase catastrophe. Combined CDK2/9 inhibition in vivo synergistically reduced PDX tumor growth. Our precision medicine pipeline provides a robust screening and validation platform to identify promising new cancer therapies. Application of this platform to colorectal cancer pinpointed CDK2/9 dual inhibition as a novel combinatorial therapy to treat colorectal cancer.
Epigenetic and Transcriptional Control of the Epidermal Growth Factor Receptor Regulates the Tumor Immune Microenvironment in Pancreatic Cancer
Authors: Li Jinyang , Yuan Salina , Norgard Robert J. , Yan Fangxue , Sun Yu H. , Kim Il-Kyu , Merrell Allyson J. , Sela Yogev , Jiang Yanqing , Bhanu Natarajan V. , Garcia Benjamin A. , Vonderheide Robert H. , Blanco Andrés , Stanger Ben Z.
Published: November 2020

Although immunotherapy has revolutionized cancer care, patients with pancreatic ductal adenocarcinoma (PDA) rarely respond to these treatments, a failure that is attributed to poor infiltration and activation of T cells in the tumor microenvironment (TME). We performed an in vivo CRISPR screen and identified lysine demethylase 3A (KDM3A) as a potent epigenetic regulator of immunotherapy response in PDA. Mechanistically, KDM3A acts through Krueppel-like factor 5 (KLF5) and SMAD family member 4 (SMAD4) to regulate the expression of the epidermal growth factor receptor (EGFR). Ablation of KDM3A, KLF5, SMAD4, or EGFR in tumor cells altered the immune TME and sensitized tumors to combination immunotherapy, whereas treatment of established tumors with an EGFR inhibitor, erlotinib, prompted a dose-dependent increase in intratumoral T cells. This study defines an epigenetic–transcriptional mechanism by which tumor cells modulate their immune microenvironment and highlights the potential of EGFR inhibitors as immunotherapy sensitizers in PDA.

Significance:

PDA remains refractory to immunotherapies. Here, we performed an in vivo CRISPR screen and identified an epigenetic–transcriptional network that regulates antitumor immunity by converging on EGFR. Pharmacologic inhibition of EGFR is sufficient to rewire the immune microenvironment. These results offer a readily accessible immunotherapy-sensitizing strategy for PDA.

This article is highlighted in the In This Issue feature, p. 521
Genetically Defined Syngeneic Mouse Models of Ovarian Cancer as Tools for the Discovery of Combination Immunotherapy
Authors: Iyer Sonia , Zhang Shuang , Yucel Simge , Horn Heiko , Smith Sean G. , Reinhardt Ferenc , Hoefsmit Esmee , Assatova Bimarzhan , Casado Julia , Meinsohn Marie-Charlotte , Barrasa M. Inmaculada , Bell George W. , Pérez-Villatoro Fernando , Huhtinen Kaisa , Hynninen Johanna , Oikkonen Jaana , Galhenage Pamoda M. , Pathania Shailja , Hammond Paula T. , Neel Benjamin G. , Farkkila Anniina , Pépin David , Weinberg Robert A.
Published: November 2020

Despite advances in immuno-oncology, the relationship between tumor genotypes and response to immunotherapy remains poorly understood, particularly in high-grade serous tubo-ovarian carcinomas (HGSC). We developed a series of mouse models that carry genotypes of human HGSCs and grow in syngeneic immunocompetent hosts to address this gap. We transformed murine-fallopian tube epithelial cells to phenocopy homologous recombination–deficient tumors through a combined loss of Trp53, Brca1, Pten, and Nf1 and overexpression of Myc and Trp53R172H, which was contrasted with an identical model carrying wild-type Brca1. For homologous recombination–proficient tumors, we constructed genotypes combining loss of Trp53 and overexpression of Ccne1, Akt2, and Trp53R172H, and driven by KRASG12V or Brd4 or Smarca4 overexpression. These lines form tumors recapitulating human disease, including genotype-driven responses to treatment, and enabled us to identify follistatin as a driver of resistance to checkpoint inhibitors. These data provide proof of concept that our models can identify new immunotherapy targets in HGSC.

Significance:

We engineered a panel of murine fallopian tube epithelial cells bearing mutations typical of HGSC and capable of forming tumors in syngeneic immunocompetent hosts. These models recapitulate tumor microenvironments and drug responses characteristic of human disease. In a Ccne1-overexpressing model, immune-checkpoint resistance was driven by follistatin.

This article is highlighted in the In This Issue feature, p. 211
Hyperuricemia and Impaired Renal Function: A Prospective Cohort Study
Authors: Aiumtrakul Noppawit , Wiputhanuphongs Puvanant , Supasyndh Ouppatham , Satirapoj Bancha
Published: November 2020

Background: Related studies have demonstrated a relationship of elevated serum uric levels with a decline in kidney function. However, limited evidence exists in a Southeast Asian community-based population. Objective: The study aimed to examine the relationship between serum uric acid levels and impaired renal function. Methods: A prospective cohort study was conducted in the Thai army health checkup population between July 1, 2006 and December 31, 2012. Inclusion criteria included age older than 20 years and baseline estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73 m2. Cox regression analysis was used to evaluate the association between incidence of impaired renal function and baseline serum uric acid quartiles. Impaired renal function was defined as eGFR <60 mL/min/1.73 m2 over 3 months. Results: A total of 9,534 participants (7,474 men and 2,060 women) were enrolled. Cox regression analysis revealed a significant association of serum uric acid level with impaired renal function in the whole population as the unadjusted hazard ratio (HR) (95% CI) of impaired renal function in second, third, and fourth quartiles were 2.1 (1.39, 3.17), 2.39 (1.6, 3.59), and 3.94 (2.71, 5.74), respectively, when compared with serum uric acid in the first quartile, respectively. After adjusting in 2 models, the HR still significantly persisted with similar magnitudes in all quartiles. Higher incidences of impaired renal function were observed among males than among females in all quartiles. Kaplan-Meier curve showed better renal survival rate in the lower quartile groups. Linear regression analysis showed that eGFR negatively correlated with serum uric acid (r = −0.213, p < 0.001). Conclusion: Our study suggests that an independent association exists of serum uric acid levels with the incidence of impaired renal function and renal progression in the Southeast Asian community-based population.
Gastric Cancer in BRCA1 Germline Mutation Carriers: Results of Endoscopic Screening and Molecular Analysis of Tumor Tissues
Authors: Avanesyan Albina A. , Sokolenko Anna P. , Ivantsov Alexandr O. , Kleshchev Maxim A. , Maydin Mikhail A. , Bizin Ilya V. , Raskin Grigory A. , Shelekhova Ksenia V. , Gorodnova Tatiana V. , Bessonov Alexandr A. , Anisimova Elena I. , Volynshchikova Olga A. , Romanko Alexandr A. , Ni Valeria I. , Broyde Robert V. , Tkachenko Oleg B. , Whitehead Aldon J. , Scherbakov Alexandr M. , Imyanitov Evgeny N.
Published: November 2020

Introduction: There is some evidence suggesting a link between BRCA1/2 germline mutations and increased risk of gastric cancer. Methods: Endoscopic screening for stomach malignancies was performed in 120 BRCA1 mutation carriers in order to evaluate the probability of detecting the tumor disease. Results: No instances of gastric cancer were revealed at the first visit. The analysis of atrophic changes performed by OLGA (Operative Link for Gastritis Assessment) criteria revealed that OLGA stages I–IV alterations were observed in 26 of 41 (63%) subjects aged >50 years as compared to 29 of 79 (37%) in younger subjects (p = 0.007, χ2 test). One BRCA1 mutation carrier developed gastric cancer 4 years after the first visit for endoscopic examination. We performed next-generation sequencing analysis for this tumor and additional 4 archival gastric cancers obtained from BRCA1/2 mutation carriers. Somatic loss of the remaining BRCA1/2 allele was observed in 3 out of 5 tumors analyzed; all of these carcinomas, but none of the malignancies with the retained BRCA1/2 copy, showed chromosomal instability. Conclusion: Taken together, these data justify further studies on the relationships between the BRCA1/2 and gastric cancer.