bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavior of the T‐Shaped Concrete‐Filled Steel Tubular Columns after Elevated Temperature
Authors: Liu Xianglong , Zhang Jicheng , Lu Hailin , Guan Ning , Xiao Jiahao , Du Guofeng
Published: March 2021

The mechanical properties of T‐shaped concrete‐filled steel tubular (TCFST) short columns under axial compression after elevated temperature are investigated in this paper. A total of 30 TCFST short columns with different temperature (T), steel ratio (α), and duration of heating (t) were tested. The TCFST column was directly fabricated by welding two rectangular steel tubes together. The study mainly investigated the failure modes, the ultimate bearing capacity, the load‐displacement, and the load‐strain performance of the TCFST short columns. Experimental results indicate that the rectangular steel tubes of the TCFST column have deformation consistency, and the failure mode consists of local crack, drum damage, and shear failure. Additionally, the influence of high temperature on the residual bearing capacity of the TCFST is significant, e.g., a higher temperature can downgrade the ultimate bearing capacity. Finally, a finite element model (FEM) is developed to simulate the performance of the TCFST short columns under elevated temperature, and the results agree with experimental values well. Overall, this investigation can provide some guidance for future studies on damage assessment and reinforcement of the TCFST columns.
Affordability of Essential Medicines and Associated Factors in Public Health Facilities of Jimma Zone, Southwest Ethiopia
Authors: Mathewos Oridanigo Eyassu , Beyene Salgedo Waju , Gebissa Kebene Feyera
Published: March 2021

Background. Affordability is one of the key dimensions for access to essential medicines, and poor affordability impedes access to treatment in health facilities. The concept of affordability is associated with the issue of impoverishment and catastrophic expenditure. The provision of affordable and appropriate essential medicines is a vital component of a well-functioning health system. Objective. The objective of this study was to assess the perceived affordability of essential medicines and associated factors in public health facilities of the Jimma Zone, Southwest Ethiopia. Methods. A facility-based cross-sectional study design was employed. The study was conducted from March 28 to April 30, 2018, in the public health facilities of Jimma Zone, Southwest Ethiopia. Based on the WHO operational package for assessing, monitoring, and evaluating a country’s pharmaceutical situations, health facilities were selected from each selected district using lower-, middle-, and higher-level criteria, making a total of 30 health facilities. For the exit interview, the total sample size was proportionally allocated for each of the selected health facilities. The data from the patient exit interview were collected using interviewer-administered structured questionnaires. The data were checked for their completeness, edited, and coded. Following this, they were entered into EpiData 3.1 and exported to SPSS version 23 for analysis. Multivariable logistic regression analysis was performed using the backward LR method to identify factors independently associated with dependent variables. Result. Six hundred and six patients participated in the study with a response rate of 97%. Among the total patients, 63.9% characterized the prescribed medicines as not affordable. The level of the health facility [AOR (95% CI) = 3.848(2.144,6.905) and

p
≤
0.001

], number of dispensed medicines [AOR (95% CI) = 0.326(0.215–0.493) and

p
≤
0.001

], occupation [AOR (95% CI) = 3.354(1.793–6.274) and

p
≤
0.001

], family income [AOR (95% CI) = 3.897(1.497–10.145) and

p
=
0.005

], place of residence [AOR (95% CI) = 2.100(1.331–3.315) and

p
=
0.001

] and number of economically dependent family members [AOR (95% CI) = 2.206(1.165–4.175) and

p
=
0.015

] were significantly associated with the perceived affordability of essential medicines. Conclusion. The average cost of dispensed medicines in the surveyed health facilities was not affordable for most of the patients. We recommend both social- and community-based health insurance schemes should be expanded to the study area.
Household Electricity Load Forecasting Based on Multitask Convolutional Neural Network with Profile Encoding
Authors: Wang Mingxin , Zheng Yingnan , Wang Binbin , Deng Zhuofu
Published: March 2021

Household load forecasting provides great challenges as a result of high uncertainty in individual consumption of load profile. Traditional models based on machine learning tried to explore uncertainty depending on clustering, spectral analysis, and sparse coding with hand craft features. Recently, deep learning skills like recurrent neural network attempt to learn the uncertainty with one-hot encoding which is too simple and not efficient. In this paper, for the first time, we proposed a multitask deep convolutional neural network for household load forecasting. The baseline of one branch is built on multiscale dilated convolutions for load forecasting. The other branch based on deep convolutional autoencoder is responsible for household profile encoding. In addition, an efficient encoding strategy for household profile is designed that serves a novel feature fusion mechanism integrated into forecasting branch. Our proposed network serves an end-to-end manner in training and inference process. Sufficient ablation studies were conducted to demonstrate effectiveness of innovations and great generalization in point and probabilistic load forecasting at household level, which provides a promising prospect in demand response.
Optimal Length of Heart Rate Variability Data and Forecasting Time for Ventricular Fibrillation Prediction Using Machine Learning
Authors: Jeong Da Un , Taye Getu Tadele , Hwang Han-Jeong , Lim Ki Moo
Published: March 2021

Ventricular fibrillation (VF) is a cardiovascular disease that is one of the major causes of mortality worldwide, according to the World Health Organization. Heart rate variability (HRV) is a biomarker that is used for detecting and predicting life-threatening arrhythmias. Predicting the occurrence of VF in advance is important for saving patients from sudden death. We extracted features from seven HRV data lengths to predict the onset of VF before nine different forecast times and observed the prediction accuracies. By using only five features, an artificial neural network classifier was trained and validated based on 10-fold cross-validation. Maximum prediction accuracies of 88.18% and 88.64% were observed at HRV data lengths of 10 and 20 s, respectively, at a forecast time of 0 s. The worst prediction accuracy was recorded at an HRV data length of 70 s and a forecast time of 80 s. Our results showed that features extracted from HRV signals near the VF onset could yield relatively high VF prediction accuracies.
Evolution Law of Coal Seam Abutment Pressure under the Influence of Shallow Buried Complex Strata: A Case Study
Authors: Zhang Buchu , Sun Dequan , Zheng Ruiliang
Published: March 2021

The evolution law of lateral abutment pressure under the condition of fully mechanized mining in shallow coal seam is studied using the change process of coal pillar stress in disturbed section as the research object. The results of physical simulation experiment show that, after coal mining, due to the collapse of coal seam roof, the overlying strata of key layer will disturb the section coal pillar to different degrees, and the sudden change of degrees of abutment pressure near the coal wall reaches the maximum. Affected by the energy released by the fracture of key stratum, the stress mutation area shifts to the coal wall at a deeper level and the range of plastic zone increases. From the perspective of the numerical simulation, according to the change characteristics of coal pillar abutment pressure in the mining process, the dynamic load process of complex roof strata is divided into three stages: the stage not affected by mining, the stage of dynamic load action, and the stage of static load. In the first stage, the lateral abutment pressure is only affected by the roadway mining, causing stress concentration in the coal body. The stress concentration coefficient is small, and the supporting stress is stable. In the second stage, with the advance of the working face, the coal seam load changes continuously owing to the movement of overlying rock in the goaf, and the lateral abutment pressure changes evidently under the influence of dynamic load. In the third stage, the overlying load forms stress concentration in the coal seam and continuously transfers to the coal wall at a deeper level, which increases the limit equilibrium area of coal body. During this period, the range of plastic zone still increases at a certain rate for a period of time and finally tends to be stable.
Pharmacological Evaluation of Antipyretic and Antioxidant Activities of 80% Methanol Root Extract and Derived Solvent Fraction of Echinops kebericho M. (Asteraceae) in Mice Model
Authors: Yimer Tesfaye , Emiru Yohannes Kelifa , Kifle Zemene Demelash , Ewunetei Amien , Adugna Meaza , Birru Eshetie Melese
Published: March 2021

Background. Toxicity and untoward effects are very ostensible in most standard drugs including antipyretic agents. Searching for conceivable antipyretic drugs with minimal toxicities and side effects from traditional plants is a growing concern to date. Echinops kebericho M. (Asteraceae) is one of the most prominent traditional medicinal plants, which is frequently testified for its traditionally claimed uses of treating fever and different infectious and noninfectious disorders by traditional healers in Ethiopian folk medicine. However, this plant has not been scientifically assessed for its traditionally claimed uses. This study therefore is aimed at investigating the antipyretic and antioxidant activities of 80% methanol root extract and the derived solvent fraction of Echinops kebericho M. in mouse models. Methods. Successive solvent maceration with increased polarity was used as the method of extractions, and chloroform, ethyl acetate, methanol, and water were used as solvents. After extraction, the crude extract and its derived solvent fractions were assessed for their antipyretic activities using yeast‐induced pyrexia while, the antioxidant activities were measured in vitro using the diphenyl‐2‐picrylhydrazyl (DPPH) assay method. Both the extract and solvent fractions were evaluated at the doses of 100, 200, and 400 mg/kg for its antipyretic activities, and the antioxidant activity was evaluated at the doses of 50, 100, 200, 400, 600, 800, and 1000 mg/kg. The positive control group was treated with standard drug (ASA 100 mg/kg), while normal saline‐receiving groups were assigned as negative control. Result. E. kebericho crude extract along with its derived solvent fractions showed statistically significant (p < 0.05, 0.01, and 0.001) temperature reduction activities. The maximum percentage of temperature reduction was observed by the highest dose (400 mg/kg) of the crude extract. The aqueous fraction also showed significantly (p < 0.05 and 0.01) higher temperature reduction than those of ethyl acetate and chloroform fractions. The free radical scavenging activities of the crude extract were also significantly high at the maximum dose, and the aqueous fraction showed the significantly highest antioxidant activity. Conclusion. In general, the data obtained from the present study clarified that the extract possessed significant antipyretic and antioxidant activities, upholding the traditionally claimed use of the plant.
Performance Analysis of Data Transmission for Joint Radar and Communication Systems
Authors: Lu Jianhua , Tian Tuanwei , Tang Yanli , Tang Bin
Published: March 2021

This paper investigates the problem of data transmission for the joint radar and communication systems (JRCSs). The performance of the JRCS is characterized by data throughput related to the radar echo data (RED) and communication data rate (CDR). Two spectral coexistence schemes are proposed based on the degree of spectrum sharing for radar and communication, i.e., the isolated subfrequency band (ISFB) and mix-used frequency band (MUFB) schemes. Firstly, the signals of radar and communication are operated on the isolated subcarriers, enabling the received signals to be processed independently and bringing the advantage of interference avoidance. Secondly, the signals of radar and communication can be jointly operated on the same subcarriers for the MUFB scheme, which enhances the spectrum efficiency. Unlike the ISFB scheme, the CDR of the MUFB scheme is maximized along with the interference from the radar signal, and meanwhile, the allocated radar power on each subcarrier is derived by maximizing the radar mutual information. Numerical results show that the MUFB scheme significantly improves the performance of data transmission over the ISFB scheme, and a significant performance gain in the data transmission can be achieved, compared to the average power allocation case.
Parameter Identification and Linear Model of Giant Magnetostrictive Vibrator
Authors: Wang Anming , Meng Jianjun , Xu Ruxun , Li Decang
Published: March 2021

A linear magnetization model is built to replace the Jiles–Atherton model in order to describe the relationship between the magnetic field intensity and the magnetization intensity of the giant magnetostrictive vibrator (GMV). The systematic modeling of the GMV is composed of three aspects, i.e., the structural mechanic model, the magnetostrictive model, and the Jiles–Atherton model. The Jiles–Atherton model has five parameters to be defined; hence, its solution is so complex that it is not convenient in application. Therefore, the immune genetic algorithm (IGA) is applied in the identification of the five parameters of the Jiles–Atherton model and it showed a higher stability compared with the identification result of the differential evolution algorithm (DEA). The identification parameters of the two algorithms were employed, respectively, to calculate the excitation force and it was found that the relative error of IGA was evidently smaller than that of DEA, indicating that the former was more reliable than the latter. According to the identification results of IGA and based on the least square method (LSM), curve-fittings to the magnetic field intensity and magnetization intensity were conducted by using the linear function. And the linear magnetization model was built to replace the Jiles–Atherton model. Research results show that the linear model of the GMV can be established by combining the linear magnetization model with the structural mechanic model as well as the giant magnetostrictive model. The linear magnetization model, which has great engineering application value, can be applied in the open-loop control of the vibrator.
Effect of Nd:YAG Laser with/without Graphite Coating on Bonding of Lithium Disilicate Glass-Ceramic to Human Dentin
Authors: Abu Hasna Amjad , Semmelmann Stephanie , Feitosa Fernanda Alves , De Souza Andrade Danilo , Tay Franklin R , Pucci Cesar Rogério
Published: March 2021

This study evaluated the effect of different surface treatments on the tensile bond strength between lithium disilicate glass-ceramics, resin cement, and dentin. Fifty truncated cone-shape glass-ceramics were divided into five groups (n = 10): G1, control: 10% hydrofluoric acid (HF); G2, Nd:YAG laser + silane; G3, Sil + Nd:YAG laser; G4, graphite + Nd:YAG laser + Sil; and G5, graphite + Sil + Nd:YAG laser. Fifty human third-molars were cut to cylindrical shape and polished to standardize the bonding surfaces. The glass-ceramic specimens were bonded to dentin with a dual-cured resin cement and stored in distilled water for 24 h at 37ºC. Tensile testing was performed on a universal testing machine (10 Kgf load cell at 1 mm/min) until failure. The bond strength values (mean ± SD) in MPa were G1 (9.4 ± 2.3), G2 (9.7 ± 2.0), G3 (6.7 ± 1.9), G4 (4.6 ± 1.1), and G5 (1.2 ± 0.3). Nd:YAG laser and HF improve the bond strength between lithium disilicate glass-ceramics, resin cement, and dentin. The application of a graphite layer prior to Nd:YAG laser irradiation negatively affects this bonding and presented inferior results.
Methods of Analysis of the Nasal Profile: A Systematic Review with Meta‐analysis
Authors: Jankowska Agnieszka , Janiszewska-Olszowska Joanna , Jedliński Maciej , Grocholewicz Katarzyna
Published: March 2021

The nose is the most prominent structure of the face, influencing facial appearance and profile. Orthodontists have an awareness of facial structures, including nasal morphology, when diagnosing and treatment planning. Maxillofacial surgeons influence facial profile by bimaxillary surgery, improving facial aesthetics and harmony. The aim of this review was to summarize the available methods of analysing nasal morphology and profile, and to assess their complexity. A literature search was conducted in PubMed, Scopus, Web of Science, and Embase using the following search terms: “nasal profile analysis”, “nasolabial angle”, and “nasal profile cephalometric” in order to select studies providing knowledge on correlations between occlusion and nasal development, differences between skeletal classes, ethnic variability, and differences between the sexes. Studies concerning genetic disorders were excluded. Finally, 17 full‐text papers were analysed, which pertained to nasolabial angle, or facial profile including the nose. Data concerning methods, ethnic group, reference landmarks used, and measurements made were extracted and placed in tables. Numerous methods of nasal profile analysis can be found in the literature. These methods describe various numbers of parameters, which have influence on facial aesthetic. Nasal parameters are correlated to skeletal class and nasolabial angle, positions of upper incisors, and maxillary inclination.
Design, Experiment, and Commissioning of the Passive Residual Heat Removal System of China’s Generation III Nuclear Power HPR1000
Authors: Li Feng , Lu Yazhe , Chu Xiao , Zheng Qiang , Wu Guanghao
Published: March 2021

In response to a station blackout accident similar to the Fukushima nuclear accident, China’s Generation III nuclear power HPR1000 designed and developed a passive residual heat removal system connected to the secondary side of the steam generator. Based on the two-phase natural circulation principle, the system is designed to bring out long-term core residual heat after an accident to ensure that the reactor is in a safe state. The steady-state characteristic test and transient start and run test of the PRS were carried out on the integrated experiment bench named ESPRIT. The experiment results show that the PRS can establish natural circulation and discharge residual heat of the first loop. China’s Fuqing no. 5 nuclear power plant completed the installation of the PRS in September 2019 and carried out commissioning work in October. This debugging is the first real-world debugging of the new design. This paper introduces the design process of the PRS debugging scheme.
The Role of Iron Tailing Powder in Ultra‐High‐Strength Concrete Subjected to Elevated Temperatures
Authors: Huang Kexin , Zhang Xindan , Lu Dong , Xu Ning , Gan Yingxin , Han Xin
Published: March 2021

Iron tailing powder (ITP) is considered to have the potential to replace cement to manufacture ultra‐high‐performance concrete (UHPC). However, the performance of UHPC with the addition of ITP after exposure to high temperatures is more complex. This investigation prepares seven UHPC formulations by introducing different contents of ITP and investigates the mechanical behavior (residual strength), bound water content, and microstructural properties (crystalline and amorphous phases, chemical structure, and morphology) of UHPC subjected to elevated temperatures. The experimental results show that the addition of ITP postpones the spalling of concrete when exposed to high temperatures. The concrete incorporating 15% ITP maintains 53.8% of its original strength at 800°C, unlike the concrete without ITP that maintains 31.6% of its original strength. The addition of ITP increases the number of micropores/cracks in concrete and helps release the vapor pressure caused by water evaporation. The findings of this investigation highlight the potential application of ITP for future UHPC design and manufacture.
Participation in an Advanced Anatomy Capstone Project Facilitates Student Involvement in the Development of an Instructional Tool for Novel Dissection
Authors: Georgetti Larry J. , Sims Ashley C. , Focht Aaron , Elcock Jamie N. , Nixon-Cave Kim , Amabile Amy H.
Published: March 2021

Introduction. Student-driven design of instructional tools within basic sciences curricula in general, and in anatomy in particular, has been shown to be both a positive educational experience for the student developers and a viable way to create quality materials for future courses. We present here a description of a student collaboration arising from participation in an advanced anatomy capstone research project, resulting in the creation of a new dissection protocol for the thoracolumbar junction dorsal primary rami and their branches. Materials and Methods. This project was initiated by two third-year doctor of physical therapy (DPT) students and involved participation from faculty and other DPT students of varying experience levels, in order to pilot and refine the tool over a two-year period. We describe the process by which the tool was developed, from the genesis of the original idea through the piloting stage. Results and Discussion. This collaboration resulted in a new instructional tool to be launched within our first-year DPT gross anatomy labs in 2022. Evaluation of the project through qualitative interviews demonstrated the learning impact on student participants. Conclusions. The success of this project shows the potential for students to be meaningfully involved in instructional tool design. The complete dissection guide, along with photos, is included and will be of particular relevance for medical and health science educators with an interest in orthopedics, neurosurgery, pain management, or physical therapy.
Perception of Tobacco Counseling and Cessation among Dental Practitioners
Authors: Alblowi Jazia A. , Mohamed Haniki
Published: March 2021

Objective. To investigate the knowledge and practice of tobacco cessation and counseling (TCC) among dental practitioners and their attitude and perceived barriers. Methods. A cross-sectional study targeted licensed dental practitioners in Jeddah, Saudi Arabia. Participants answered a pretested and validated self-administered questionnaire consisted of demographic data; smoking status; knowledge of tobacco hazards, attitude, and practice; and perceived barriers of tobacco cessation counseling. Result. Among the total sample of 529, response rate was 72.2% (mean age (34.20 ± 9.38 years), males (42.4%), and current smokers (23.8%)). Only 13.2% received formal training on TCC. Around (57.1%) reported smoking of dental team as an obstacle for TCC. Half of the participants (49.9%) reported patient’s resistance as barrier to TCC. Others (45%–48%) reported insufficient time, knowledge, or training for TCC. Professional responsibility and willingness to provide cessation services constituted the highest median. Conclusion. The majority showed willingness to participate in TCC. Lack of training, smoking status of providers, females, inadequate materials, and patients’ resistance were the most common barriers. Education and training on TCC are recommended and should be allowed as a routine practice in dentistry.
A New Hybrid Model for Hourly Solar Radiation Forecasting Using Daily Classification Technique and Machine Learning Algorithms
Authors: Ali-Ou-Salah Hamza , Oukarfi Benyounes , Bahani Khalid , Moujabbir Mohammed
Published: March 2021

Photovoltaic power generation depends significantly on solar radiation, which is variable and unpredictable in nature. As a result, the production of electricity from photovoltaic power cannot be guaranteed permanently during the operational phase. Forecasting global solar radiation can play a key role in overcoming this drawback of intermittency. This paper proposes a new hybrid method based on machine learning (ML) algorithms and daily classification technique to forecast 1 h ahead of global solar radiation in the city of Évora. Firstly, several comparative studies have been done between random forest (RF), gradient boosting (GB), support vector machines (SVM), and artificial neural network (ANN). These comparisons were made using annual, seasonal, and daily testing sets in order to determine the best ML algorithm under different meteorological conditions. Subsequently, the daily classification technique has been applied to classify the original training set into sunny and cloudy training subsets in order to enhance the forecasting accuracy. The evaluation of the proposed ML algorithms was carried out using the normalized root mean square error (nRMSE) and the normalized absolute mean error (nMAE). The results of the seasonal comparison show that the RF model performs well for spring and autumn seasons with nRMSE equaling 22.53% and 23.42%, respectively. While the SVR model gives good results for winter and summer seasons with nRMSE equaling 24.31% and 8.41%, respectively. In addition, the daily comparison demonstrates that the RF model performs well for cloudy days with nRMSE = 41.40%, while the SVR model yields good results for sunny days with nRMSE = 8.88%. The results show that the daily classification technique enhances the forecasting accuracy of ML models. Furthermore, this study demonstrates that the forecasting accuracy of ML algorithms depends significantly on sky conditions.
Generalized Type-I Hybrid Censoring Scheme in Estimation Competing Risks Chen Lifetime Populations
Authors: Sayed-Ahmed Neveen , Jawa Taghreed M. , Aloafi Tahani A. , Bayones F. S. , Elhag Azhari A. , Bouslimi J. , Abd-Elmougod G. A.
Published: March 2021

Different types of censoring scheme are investigated; however, statistical inference on censoring scheme which can save the ideal test time and the minimum number of failures is needed. The generalized type-I hybrid censoring scheme (GHCS) solves this problem. Competing the risk models under the GHCS when time to failure has Chen lifetime distribution (CD) is adopted in this research with consideration of only two cases of failure. Partially step-stress accelerated life tests (ALTs) are applied to obtain enough failure times in a small period to achieve a highly reliable product. The problem of parameter estimation under maximum likelihood (ML) and Bayes methods is discussed. The asymptotic confidence interval as well as the Bayes credible interval is constructed. The validity of theoretical results is assessed and compared through simulation study. Finally, brief comments are reported to describe the behaviour of the estimation results.
[Retracted] Pentoxifylline Can Reduce the Inflammation Caused by LPS after Inhibiting Autophagy in RAW264.7 Macrophage Cells
Authors: Ruan Danping , Deng Sinan , Liu Zhonglong , He Jie
Published: March 2021

Pentoxifylline (PTX), as a methylxanthine derivative and nonspecific phosphodiesterase inhibitor, has the characteristics of anti‐inflammatory and partial inflammatory process inhibition. However, the regulatory effect of PTX on inflammatory cytokines is unclear. Autophagy can regulate the activation of inflammasomes and then inhibit inflammation as previously described. Our study attempts to explore the relationship between autophagy and PTX‐mediated regulation of inflammasome suppression. Macrophage‐like RAW264.7 cells were studied as the in vitro macrophage model. We investigated the anti‐inflammatory effect caused by PTX with time and dose response against the LPS‐induced inflammatory factors (TNF‐α, IL‐1β). Western blot detected the levels of autophagy‐related proteins Beclin‐1 and LC3, as well as the signal pathways of AMPK and p‐AMPK. Fluorescence microscope and transmission electron microscope were used to observe the autophagy bodies in cells influenced by PTX. The autophagy in cells inhibited by PTX exhibited dose‐ and time‐dependent effects, and PTX alleviated LPS‐induced inflammation caused by retarded autophagy. Furthermore, in RAW264.7 macrophage cells, our data indicated that AMPK signaling perhaps functioned importantly in repressed autophagy. In addition, in RAW264.7 macrophages, our data suggested that AMPK signaling might play an important role in inhibiting autophagy during the process of PTX ameliorating LPS‐mediated inflammation.
Use of Antidepressants among Patients Diagnosed with Depression: A Scoping Review
Authors: Marasine Nirmal Raj , Sankhi Sabina , Lamichhane Rajendra , Marasini Nabin Raj , Dangi Nim Bahadur
Published: March 2021

Introduction. Depression is a major global health problem with a relatively high lifetime prevalence and significant disability. Antidepressants are the most effective medications used for the treatment of depression. Hence, this study is aimed at summarizing the studies on antidepressant use among patients diagnosed with depression. Method. PubMed, Embase, Web of Science, Scopus, and Google Scholar were searched for literature (2000‐2019) using keywords such as depression, drug utilization, antidepressants, prescription, serotonin reuptake inhibitor, serotonin and norepinephrine reuptake inhibitor, tricyclic antidepressants, and atypical antidepressants. Results. Antidepressant users were mostly females, married people, housewives, lower‐income people, employees, and highly educated people, as they were found to be more prone to develop depression than their counterparts. Selective serotonin reuptake inhibitors (SSRIs), such as sertraline, were most commonly prescribed among depressive patients. Conclusion. Our study suggested that out of five major antidepressant drugs available for the treatment of depression, selective serotonin reuptake inhibitors are preferred over others because of their better side effects and tolerability profile.
BRDF Model of Mars Simulation Soil and Its Comparison with BRDF of Earth Sand
Authors: Yang Yu-Feng , Han Xiang , Jiang Ming-Bo , Han An-Li , Li Wen-Shuai
Published: March 2021

In this paper, a seven‐parameter BRDF model with double‐peak characteristic, which could fit double‐peak data, was adopted to fit the BRDF of Mars simulation soil. At the same time, the three‐dimensional figure of the original data of the sample and the three‐dimensional curve of the fitted curve were given. The results proved that the model worked well for this type of data. In addition, the experimental data of four kinds of earth sand samples with different roughness were also fitted and analyzed. It was found that the model still had a good fitting effect on such data. At last, the Mars simulation soil and the four kinds of earth sand samples with different roughness were compared horizontally and vertically. Moreover, the double‐peak characteristics and other properties of the Mars simulation soil and the earth sand were analyzed under the same and different roughness.
Pericarditis Caused by Enterococcus faecium with Acute Liver Failure Treated by a Multifaceted Approach including Antimicrobials and Hemoadsorption
Authors: Köhler Thomas , Pletz Mathias W. , Altmann Simon , Kirchner Carmen , Schwier Elke , Henzler Dietrich , Winde Günther , Eickmeyer Claas
Published: March 2021

Background. Sepsis and septic shock are still life-threatening diseases with a high mortality rate. We report a complex case of peritonitis with pericarditis and acute liver failure caused by septic shock. Potentially hepatotoxic antibiotic therapy levels were monitored using the liver maximum capacity (LiMAx®) test, and standard treatment was supplemented by adjunctive hemoadsorption with CytoSorb®. Case Presentation. The case features a 29-year-old woman with a history of Crohn’s disease and cachexia. Peritonitis caused by Enterococcus faecium was diagnosed later due to an ileum perforation. The hematogenic spread led to pericarditis. In addition, sepsis-related acute liver failure complicated antimicrobial therapy further. The combination of standard therapy, anti-infective medication, and blood purification was associated with inflammation control, hemodynamic stabilization, and a concomitant decrease in vasopressor support. An efficient, sustained reduction in plasma bilirubin levels was achieved while maintaining liver function. Conclusions. This case shows how complex infectious diseases with an atypical infectious focus resulting in septic shock can be successfully treated. A combination of antimicrobial (tigecycline and caspofungin) and long-term adjunctive hemoadsorption therapy was administered while hepatotoxic antibiotic medication was monitored by liver function testing.
The Association between Five Genetic Variants in MicroRNAs (rs2910164, rs11614913, rs3746444, rs11134527, and rs531564) and Cervical Cancer Risk: A Meta‐Analysis
Authors: Liu Jia , Dong Peng , Zhou Liane , Wang Shijun
Published: March 2021

The objective of this study was to conduct a meta‐analysis to systematically summarize and investigate the association of miRNA‐124 rs531564, miRNA‐218 rs11134527, miRNA‐146a rs2910164, miRNA‐196a2 rs11614913, and miRNA‐499 rs3746444 polymorphisms with cervical cancer. A systematic review was performed to identify relevant studies using Embase and PubMed databases. A chi‐square‐based Q‐test combined with the inconsistency index (I2) was used to check the heterogeneity between studies. A total of six case‐control studies on rs2910164 and rs11614913, 4 studies on rs3746444 and rs11134527, and three studies on rs531564 were included. No evidence of association was found between miR‐146a rs2910164, miR‐196a2 rs11614913, miRNA‐499 rs3746444, and miR‐218 rs11134527 polymorphisms and cervical cancer risk in all the genetic models. The miR‐124 rs531564 polymorphism was associated with a statistically increased risk of cervical cancer in a homozygote model (CC vs. GG: OR = 2.87, 95% CI: 1.40‐5.91, PH = 0.887), dominant model (GC/CC vs. GG: OR = 1.38, 95% CI: 1.07‐1.80, PH = 0.409), and recessive model (CC vs. GC/GG: OR = 2.26, 95% CI: 1.58‐3.23, PH = 0.979). However, this finding should be interpreted with caution for limited samples and heterogeneity. Large‐scale and well‐designed studies are needed to validate our result.
Endoscopic Treatment of Zenker’s Diverticulum: Comparable Treatment Outcomes in Treatment-Naïve and Pretreated Patients
Authors: Manzeneder Johannes , Römmele Christoph , Manzeneder Carolin , Ebigbo Alanna , Messmann Helmut , Goelder Stefan Karl
Published: March 2021

Background and Aims. Flexible endoscopic treatment plays an important role in the treatment of Zenker’s diverticulum (ZD). This study analyzes long-term symptom control and the rate of adverse events in treatment-naïve patients and patients with recurrence, using the stag beetle knife junior (sb knife jr). Methods. From August 2013 to May 2019, 100 patients with symptomatic ZD were treated with flexible endoscopy using the sb knife jr. Before treatment, as well as 1 and 6 months afterwards, symptoms were obtained by a nine-point questionnaire, with symptoms weighted from 0 to 4. Results. Overall, 126 interventions were performed. The median follow-up period was 41 months (range 7-74). For the three most frequent symptoms, regurgitation, dysphagia, and dry cough, a significant reduction of the mean score could be achieved, from 2.85/3.45/2.85 before the initial treatment to 0.56/1.09/0.98 6 months later. 17 patients were retreated because of recurrence. Out of these, 12 patients underwent a 2nd, 4 patients a 3rd, and 1 patient a 4th session, respectively. The mean dysphagia score for successfully treated patients could be reduced from initially 2.34 to 0.49/0.33/0.67 after the 1st/2nd/3rd session, the frequency of dysphagia from 3.45 to 0.92/1.00/1.33, and the score for regurgitations from 2.85 to 0.35/1.00/0.67. In first-line treatment, as well as in retreatment, no severe adverse event occurred. Conclusion. Patients with ZD can be treated safely and effectively with the sb knife jr. Retreatment leads to equal symptom relief as compared to a successful first-line treatment and is not associated with a higher rate of adverse events.
Single-Cell RNA Sequencing Reveals the Cellular Origin and Evolution of Breast Cancer in BRCA1 Mutation Carriers
Authors: Hu Li , Su Liming , Cheng Hainan , Mo Chunling , Ouyang Tao , Li Jinfeng , Wang Tianfeng , Fan Zhaoqing , Fan Tie , Lin Benyao , Zhang Jianguang , Xie Yuntao
Published: March 2021

The cell of origin and the development of breast cancer are not fully elucidated in BRCA1 mutation carriers, especially for estrogen receptor (ER)–positive breast cancers. Here, we performed single-cell RNA sequencing (RNA-seq) on 82,122 cells isolated from the breast cancer tissues and adjacent or prophylactic normal breast tissues from four BRCA1 mutation carriers and three noncarriers. Whole-exome sequencing was performed on breast tumors from the four BRCA1 mutation carriers; for validation, bulk RNA-seq was performed on adjacent normal breast tissues from eight additional BRCA1 mutation carriers and 14 noncarriers. Correlation analyses suggested that breast cancers in BRCA1 mutation carriers might originate from luminal cells. The aberrant luminal progenitor cells with impaired differentiation were significantly increased in normal breast tissues in BRCA1 mutation carriers compared with noncarriers. These observations were further validated by the bulk RNA-seq data from additional BRCA1 mutation carriers. These data suggest that the cell of origin of basal-like breast tumors (ERneg) in BRCA1 mutation carriers might be luminal progenitor cells. The expression of TP53 and BRCA1 was decreased in luminal progenitor cells from normal breast tissue in BRCA1 mutation carriers, which might trigger the basal/mesenchymal transition of luminal progenitors and might result in basal-like tumor development. Furthermore, ERhigh luminal tumors might originate from mature luminal cells. Our study provides in-depth evidence regarding the cells of origin of different breast cancer subtypes in BRCA1 mutation carriers.

Significance:

Single-cell RNA-seq data indicate that basal-like breast cancer (ERneg) might originate from luminal progenitors, and ERhigh luminal breast cancer might originate from mature luminal cells in BRCA1 mutation carriers.
Alterations in the Global Proteome and Phosphoproteome in Third Generation EGFR TKI Resistance Reveal Drug Targets to Circumvent Resistance
Authors: Zhang Xu , Maity Tapan K. , Ross Karen E. , Qi Yue , Cultraro Constance M. , Bahta Meriam , Pitts Stephanie , Keswani Meghana , Gao Shaojian , Nguyen Khoa Dang P. , Cowart Julie , Kirkali Fatos , Wu Cathy , Guha Udayan
Published: March 2021

Lung cancer is the leading cause of cancer mortality worldwide. The treatment of patients with lung cancer harboring mutant EGFR with orally administered EGFR tyrosine kinase inhibitors (TKI) has been a paradigm shift. Osimertinib and rociletinib are third-generation irreversible EGFR TKIs targeting the EGFR T790M mutation. Osimertinib is the current standard of care for patients with EGFR mutations due to increased efficacy, lower side effects, and enhanced brain penetrance. Unfortunately, all patients develop resistance. Genomic approaches have primarily been used to interrogate resistance mechanisms. Here we characterized the proteome and phosphoproteome of a series of isogenic EGFR-mutant lung adenocarcinoma cell lines that are either sensitive or resistant to these drugs, comprising the most comprehensive proteomic dataset resource to date to investigate third generation EGFR TKI resistance in lung adenocarcinoma. Unbiased global quantitative mass spectrometry uncovered alterations in signaling pathways, revealed a proteomic signature of epithelial–mesenchymal transition, and identified kinases and phosphatases with altered expression and phosphorylation in TKI-resistant cells. Decreased tyrosine phosphorylation of key sites in the phosphatase SHP2 suggests its inhibition, resulting in subsequent inhibition of RAS/MAPK and activation of PI3K/AKT pathways. Anticorrelation analyses of this phosphoproteomic dataset with published drug-induced P100 phosphoproteomic datasets from the Library of Integrated Network-Based Cellular Signatures program predicted drugs with the potential to overcome EGFR TKI resistance. The PI3K/MTOR inhibitor dactolisib in combination with osimertinib overcame resistance both in vitro and in vivo. Taken together, this study reveals global proteomic alterations upon third generation EGFR TKI resistance and highlights potential novel approaches to overcome resistance.

Significance:

Global quantitative proteomics reveals changes in the proteome and phosphoproteome in lung cancer cells resistant to third generation EGFR TKIs, identifying the PI3K/mTOR inhibitor dactolisib as a potential approach to overcome resistance.
Integrated Screens Identify CDK1 as a Therapeutic Target in Advanced Gastrointestinal Stromal Tumors
Authors: Lu Xiaojing , Pang Yuzhi , Cao Hui , Liu Xiaoxiao , Tu Lin , Shen Yanying , Jia Xiaona , Lee Jen-Chieh , Wang Yuexiang
Published: March 2021

Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling therapeutic targets in gastrointestinal stromal tumor (GIST), and treatment with the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with advanced GIST. Polyclonal emergence of KIT/PDGFRA secondary mutations is the main mechanism of imatinib progression, making it challenging to overcome KIT/PDGFRA-inhibitor resistance. It is unclear whether there are other therapeutic targets in advanced GIST. Using genome-wide transcriptomic profiling of advanced versus early-stage GIST and CRISPR knockout functional screens, we demonstrate that CDK1 is frequently highly expressed in advanced GIST but not in early-stage GIST across three patient cohorts. High expression of CDK1 was associated with malignancy in GIST. CDK1 was critically required for advanced GIST, including imatinib-resistant GIST. CDK1 ablation led to robust proliferation inhibition. A mass spectrometry-based proteomics screen further revealed that AKT is a novel substrate of CDK1 kinase in GIST. CDK1 bound AKT and regulated its phosphorylation, thereby promoting GIST proliferation and progression. Importantly, a pharmacologic inhibitor of CDK1, RO-3306, disrupted GIST cell proliferation in CDK1 highly expressed GIST but not in CDK1-negative GIST cells and nontransformed fibroblast cells. Treatment with RO-3306 reduced tumor growth in both imatinib-resistant and imatinib-sensitive GIST xenograft mouse models. Our findings suggest that CDK1 represents a druggable therapeutic target in GIST and warrants further testing in clinical trials.

Significance:

These findings propose CDK1 as a novel cell-cycle–independent vulnerability in gastrointestinal stromal tumors, representing a new therapeutic opportunity for patients with advanced disease.
Eribulin Plus Pembrolizumab in Patients with Metastatic Triple-Negative Breast Cancer (ENHANCE 1): A Phase Ib/II Study
Authors: Tolaney Sara M. , Kalinsky Kevin , Kaklamani Virginia G. , D'Adamo David R. , Aktan Gursel , Tsai Michaela L. , O'Regan Ruth M. , Kaufman Peter A. , Wilks Sharon T. , Andreopoulou Eleni , Patt Debra A. , Yuan Yuan , Wang Grace , Savulsky Claudio , Xing Dongyuan , Kleynerman Ella , Karantza Vassiliki , Diab Sami
Published: March 2021

Purpose:

As monotherapies, eribulin (chemotherapy) and pembrolizumab (immunotherapy) have shown promise for patients with metastatic triple-negative breast cancer (mTNBC). This phase Ib/II study examined eribulin plus pembrolizumab as a potential mTNBC treatment in first-line and later-line settings.

Patients and Methods:

In this open-label, single-arm, phase Ib/II study, eligible patients had mTNBC, measurable disease, and ≤2 prior systemic anticancer therapies in the metastatic setting. Patients were enrolled by number of prior systemic anticancer therapies (stratum 1: 0 vs stratum 2: 1–2) in the metastatic setting and further analyzed by tumor programmed death-ligand 1 (PD-L1) expression status. All patients received intravenous eribulin 1.4 mg/m2 on day 1 and day 8, plus intravenous pembrolizumab 200 mg on day 1, of 21-day cycles. The primary objectives were the safety, tolerability, and objective response rate (ORR) of this combination.

Results:

The study included 167 patients (phase Ib, n = 7; phase II, n = 160). The most common treatment-emergent adverse events were fatigue (66%), nausea (58%), peripheral sensory neuropathy (41%), alopecia (40%), and constipation (37%). ORRs were 25.8% [95% confidence interval (CI): 15.8–38.0] for stratum 1 (n = 66) and 21.8% (95% CI: 14.2–31.1) for stratum 2 (n = 101). Patients with PD-L1–positive tumors (combined positive score ≥1) had numerically higher ORR than those with PD-L1–negative tumors, particularly in stratum 1 [stratum 1: 34.5% (95% CI: 17.9–54.3) vs 16.1% (95% CI: 5.5–33.7); stratum 2, 24.4% (95% CI: 12.9–39.5) vs 18.2% (95% CI: 8.2–32.7)].

Conclusions:

Eribulin plus pembrolizumab was generally well tolerated and showed promising antitumor activity in mTNBC. Efficacy outcomes appeared influenced by line of therapy and PD-L1 status.
A Randomized Phase II Study of Androgen Deprivation Therapy with or without Palbociclib in RB-positive Metastatic Hormone-Sensitive Prostate Cancer
Authors: Palmbos Phillip L. , Daignault-Newton Stephanie , Tomlins Scott A. , Agarwal Neeraj , Twardowski Przemyslaw , Morgans Alicia K. , Kelly Wm. Kevin , Arora Vivek K. , Antonarakis Emmanuel S. , Siddiqui Javed , Jacobson Jon A. , Davenport Matthew S. , Robinson Dan R. , Chinnaiyan Arul M. , Knudsen Karen E. , Hussain Maha
Published: March 2021

Purpose:

Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, blocks proliferation in a RB and cyclin D–dependent manner in preclinical prostate cancer models. We hypothesized that cotargeting androgen receptor and cell cycle with palbociclib would improve outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Patients and Methods:

A total of 60 patients with RB-intact mHSPC were randomized (1:2) to Arm 1: androgen deprivation (AD) or Arm 2: AD + palbociclib. Primary endpoint was PSA response rate (RR) after 28 weeks of therapy. Secondary endpoints included safety, PSA, and clinical progression-free survival (PFS), as well as PSA and radiographic RR. Tumors underwent exome sequencing when available. Circulating tumor cells (CTC) were enumerated at various timepoints.

Results:

A total of 72 patients with mHSPC underwent metastatic disease biopsy and 64 had adequate tissue for RB assessment. A total of 62 of 64 (97%) retained RB expression. A total of 60 patients initiated therapy (Arm 1: 20; Arm 2: 40). Neutropenia was the most common grade 3/4 adverse event in Arm 2. Eighty percent of patients (Arm 1: 16/20, Arm 2: 32/40; P = 0.87) met primary PSA endpoint ≤4 ng/mL at 28 weeks. PSA undetectable rate at 28 weeks was 50% and 43% in Arms 1 and 2, respectively (P = 0.5). Radiographic RR was 89% in both arms. Twelve-month biochemical PFS was 69% and 74% in Arms 1 and 2, respectively (P = 0.72). TP53 and PIK3 pathway mutations, 8q gains, and pretreatment CTCs were associated with reduced PSA PFS.

Conclusions:

Palbociclib did not impact outcome in RB-intact mHSPC. Pretreatment CTC, TP53 and PIK3 pathway mutations, and 8q gain were associated with poor outcome.