bluuebunny/crossref_metadata_2025 huggingface dataset:
[Retracted] Complex System of Vertical Baduanjin Lifting Motion Sensing Recognition under the Background of Big Data
Authors: Zhang Yan , Kamruzzaman M. M. , Feng Lu
Published: February 2021

Nowadays, the development of big data is getting faster and faster, and the related research on motion sensing recognition and complex systems under the background of big data is gradually being valued. At present, there are relatively few related researches on vertical Baduanjin in the academic circles; research in this direction can make further breakthroughs in motion sensor recognition. In order to carry out related action recognition research on the lifting action of vertical Baduanjin, this paper uses sensor technology to collect the motion video image of vertical Baduanjin based on the background of big data and uses action recognition technology and related algorithms to obtain the action. Recognize the video image to obtain the data, get the acceleration, angular velocity, and EMG data, and count the end time and duration according to the change of the action. According to the data table and graph change trend compiled at the end of the experiment, we can see the following: after the data is preprocessed, the acceleration signal change range is limited to [−1, 1], and the acceleration change has a clear directionality; and, after 15 lifts of the detected object, its angular velocity in X‐axis direction is basically negative. However, when the ninth lift is performed, the angular velocity of the movement in X‐axis direction is 36.09, the largest of all angular velocities. When performing the 15th lifting action, the angular velocity of this action in Z‐axis direction is −26.05, which is the smallest of all angular velocities. The longest duration of the left muscle discharge during the lifting action of the subject is 15.24 for the tibial anterior muscle and 8.91 for the external oblique muscle with the shortest duration. The longest discharge duration of the right muscle is also the tibial anterior muscle with 12.15, and the shortest duration is the erector spinae with 8.79.
Fault Recognition of Indicator Diagrams Based on the Dynamic Time Warping Distance of Differential Curves
Authors: Du Yi , Zhao Peng , Zhang Ting
Published: February 2021

Oil recovery with pumping units is widely used in oilfield development at present. The management level of pumping units is related to the overall economic benefit of oilfield. In order to effectively control the production management of pumping wells, it is necessary to take all the production data to formulate a reasonable working system and make continuous analyses about the daily management level of pumping wells. The analysis and interpretation of the indicator diagram is a direct understanding way about the situation of deep well pumps in petroleum engineering. However, the complicated practical oilfield conditions often lead to the distortion of regular indicator diagrams, resulting in the low efficiency of fault-type diagnosis and wrong recognition. A new method of identifying the fault type of indicator diagrams is proposed by using the dynamic time warping (DTW) distance, through which a two-dimensional indicator diagram is transformed into a one-dimensional differential curve. The experimental results of real indicator diagrams show that the method is effective for the type diagnosis of indicator diagrams with high accuracy and fast speed.
Spreading Dynamics of a 2SIH2R, Rumor Spreading Model in the Homogeneous Network
Authors: Wang Yan , Qing Feng , Chai Jian-Ping , Ni Ye-Peng
Published: February 2021

With the rapid development of social network in recent years, the threshold of information dissemination has become lower. Most of the time, rumors, as a special kind of information, are harmful to society. And once the rumor appears, the truth will follow. Considering that the rumor and truth compete with each other like light and darkness in reality, in this paper, we study a rumor spreading model in the homogeneous network called 2SIH2R, in which there are both spreader1 (people who spread the rumor) and spreader2 (people who spread the truth). In this model, we introduced discernible mechanism and confrontation mechanism to quantify the level of people′s cognitive abilities and the competition between the rumor and truth. By mean‐field equations, steady‐state analysis, and numerical simulations in a generated network which is closed and homogeneous, some significant results can be given: the higher the discernible rate of the rumor, the smaller the influence of the rumor; the stronger the confrontation degree of the rumor, the smaller the influence of the rumor; the larger the average degree of the network, the greater the influence of the rumor but the shorter the duration. The model and simulation results provide a quantitative reference for revealing and controlling the spread of the rumor.
Depression among Patients with Schizophrenia in Ethiopian Mental Health Hospital: Association with Sociodemographic and Clinical Variables: A Cross-Sectional Study
Authors: Tariku Mandaras , Ali Tilahun , Misgana Tadesse , Hajure Mohammedamin , Asfaw Henock
Published: February 2021

Background. Depression is a significant contributor to the global burden of disease and affects all individuals throughout their lifetime. Patients with schizophrenia are frequently attacked by depression during their total illness duration. Presence of comorbid depression in schizophrenia makes the patients more deteriorating and disabling course and poor outcome. Aim of the Study. To determine the prevalence of depression and highlight the associated sociodemographic and clinical factors in patients with schizophrenia in a specialized hospital in Addis Ababa, Ethiopia. Setting. This study was conducted at Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia. Methods. An institutional based cross-sectional study was conducted from May to June 2018. Depression was measured by Calgary Depression Scale for Schizophrenia on 455 samples of patient with schizophrenia and systematic sampling was used to select the study participants. Oslo Social Support Scale and Alcohol, Smoking, and Substance Involvement Screening Test were used to assess social support and substance use factors, respectively. A bivariable and multivariable logistic regression analysis model was performed to control the confounding factors. Odds ratio (OR) with the corresponding 95% confidence interval (95% CI) was determined to evaluate the strength of association. Results. A total of 445 patients responded to the questionnaire, which yields a response rate of 97.8%. The Magnitude of depression among schizophrenia patients was 24.9%. A multivariable logistic regression analysis model showed that being female [AOR 2.00, 95% CI: 1.25-3.18], divorced/widowed [AOR 2.39, 95% CI: 1.04-5.49], current substance use [AOR 1.95, 95% CI: 1.17-3.25], and poor social support [AOR 2.75, 95% CI: 1.35-5.61] were significantly associated with depression in schizophrenia. Conclusion. The magnitude of depression among schizophrenia was 24.9%. Being female, divorced/widowed, current substance use, and poor social support were associated with depression among patients with schizophrenia. Regular screening and prompt management of depressive symptoms among patients with schizophrenia is of particular importance to reduce the burden of the condition.
Exacerbation of Subthreshold PTSD Symptoms in a Great East Japan Earthquake Survivor in the Context of the COVID-19 Pandemic
Authors: Hori Arinobu , Sawano Toyoaki , Ozaki Akihiko , Tsubokura Masaharu
Published: February 2021

Background. In 2011, the people of Fukushima, Japan, experienced the Great East Japan Earthquake (GEJE), a complex disaster of earthquake, tsunami, and nuclear accident. Its residents are experiencing a second global disaster, a COVID-19 pandemic in 2020. Objective. In this article, we aimed at discussing the effects of subthreshold PTSD in a previous disaster on an exacerbation of PTSD symptoms in another disaster. Method. We present a case of subthreshold PTSD in the context of a nuclear accident and exacerbation of symptoms due to the COVID-19 pandemic. Results. Exacerbation of subthreshold PTSD symptoms was likely due to the reemergence of an urgent atmosphere similar to the previously experienced traumatic event. Conclusions. PTSD may occur not only in those who experience the actual life-threatening like ICU admission but in those who experience the atmospheric change of society. This case demonstrated the characteristics of subthreshold PTSD caused by two disasters that shared a similar sense of insecurity, the scale of impact on the society, invisibility of the threat, restricted movement, and authoritative conflicts. These commonalities led to a recurrence and exacerbation of initial symptoms. This finding should be shared with those involved in the care system for victims’ mental health suffering from a large-scale disaster, and we need further research about the issue.
Effectiveness of Glucocorticoids in Acute Respiratory Distress Syndrome: An Umbrella Review
Authors: Abate Semagn Mekonnen , Mulugeta Kassim Hailemariam , Basu Bivash , Nega Solomon
Published: February 2021

Objectives. Acute respiratory distress syndrome is a very challenging condition that is associated with high morbidity and mortality. This review was intended to evaluate evidence on the effectiveness of glucocorticoid treatment for acute respiratory distress syndrome. Method. A comprehensive search strategy was conducted on PubMed/Medline, Cochrane Library, Science Direct, and LILACS. Data extraction was carried out by two independent reviewers using a customized checklist. The quality of each systematic review was assessed by two independent reviewers using an AMSTAR tool, and the overall quality of evidence was generated with online GRADEpro GDT software for primary and secondary outcomes. Results. The umbrella review included nine systematic reviews and meta-analysis and one narrative review with 8491 participants. The methodological quality of the included studies was moderate-to-high quality. The overall quality of evidence and recommendations varied form high to very low. Conclusion. There is high-to-moderate quality evidence that early low-dose prolonged glucocorticoid therapy reduces mortality in ARDS. However, randomized controlled trials with large sample sizes to address ventilator-free days, the incidence of infection, and other glucocorticoid-associated adverse events are required as the quality of evidence for these secondary outcomes which were low to very low. Registration. This umbrella review was registered in PROSPERO, the International Prospective Register of Systematic Reviews (CRD42019130539).
Enhanced Seismic Structural Reliability on Reinforced Concrete Buildings by Using Buckling Restrained Braces
Authors: Baca Victor , Bojórquez Juan , Bojórquez Edén , Leyva Herian , Reyes-Salazar Alfredo , Ruiz Sonia E. , Formisano Antonio , Palemón Leonardo , Chávez Robespierre , Barraza Manuel
Published: February 2021

The control of vibrations and damage in traditional reinforced concrete (RC) buildings under earthquakes is a difficult task. It requires the use of innovative devices to enhance the seismic behavior of concrete buildings. In this paper, we design RC buildings with buckling restrained braces (BRBs) to achieve this objective. For this aim, three traditional RC framed structures with 3, 6, and 9 story levels are designed by using the well‐known technique nondominated sorting genetic algorithm (NSGA‐II) in order to reduce the cost and maximize the seismic performance. Then, equivalent RC buildings are designed but including buckling restrained braces. Both structural systems are subjected to several narrow‐band ground motions recorded at soft soil sites of Mexico City scaled at different levels of intensities in terms of the spectral acceleration at first mode of vibration of the structure Sa(T1). Then, incremental dynamic analysis, seismic fragility, and structural reliability in terms of the maximum interstory drift are computed for all the buildings. For the three selected structures and the equivalent models with BRBs, it is concluded that the annual rate of exceedance is considerably reduced when BRBs are incorporated. For this reason, the structural reliability of the RC buildings with BRBs has a better behavior in comparison with the traditional reinforced concrete buildings. The use of BRBs is a good option to improve strength and seismic behavior and hence the structural reliability of RC buildings subjected to strong earthquake ground motions.
Risk Factors for Chikungunya Virus Outbreak in Somali Region of Ethiopia, 2019: Unmatched Case-Control Study
Authors: Alayu Mikias , Teshome Tesfalem , Amare Hiwot , Kinde Solomon , Belay Desalegn , Assefa Zewdu
Published: February 2021

Background. Chikungunya virus is a ribonucleic acid (RNA) virus transmitted by a mosquito bite. Chikungunya virus outbreaks are characterized by rapid spread, and the disease manifests as acute fever. This study aimed at determining risk factors for chikungunya virus outbreak to apply appropriate prevention and control measures. Methods. Unmatched case-control study was performed to identify risk factors of chikungunya outbreak in Somali region of Ethiopia in 2019. Cases and controls were enrolled with 1 : 2 ratio. All cases during the study period (74 cases) and 148 controls were included in the study. Bivariate and multivariable analyses were implemented. The serum samples were tested by real-time polymerase chain reaction at Ethiopian Public Health Institute Laboratory. Results. A total of 74 chikungunya fever cases were reported starting from 19th May 2019 to 8th June 2019. Not using bed net at daytime sleeping (adjusted odds ratio (AOR): 20.8; 95% confidence interval (CI): 6.4–66.7), presence of open water holding container (AOR: 4.0; CI: 1.2–3.5), presence of larvae in water holding container (AOR: 4.8; CI: 1.4–16.8), ill person with similar signs and symptoms in the family or neighbors (AOR: 27.9; CI: 6.5–120.4), and not wearing full body cover clothes (AOR: 8.1; CI: 2.2–30.1) were significant risk factors. Conclusion. Not using bed net at daytime sleeping, presence of open water holding container, presence of larvae in water holding container, ill person with similar signs and symptoms in the family or neighbors, and not wearing full body cover clothes are risk factors for chikungunya virus outbreak.
Effective Lipid Nanocarriers Based on Linseed Oil for Delivery of Natural Polyphenolic Active
Authors: Coc Lucia Marina Cristina , Lacatusu Ioana , Badea Nicoleta , Barbinta-Patrascu Marcela Elisabeta , Meghea Aurelia
Published: February 2021

The main purpose of the present research was to test the ability of nanostructured lipid carriers (NLCs) to efficiently host a hydrophilic polyphenol active with health-promoting activities (caffeic acid (CA)). The caffeic acid-loaded lipid nanocarriers (CA-NLCs) were obtained by high-pressure homogenization technique using a surfactant mixture of Tween 20 and L-α-phosphatidylcholine in association with a lipid mixture of linseed oil, hexadecyl palmitate, and glycerol monostearate. In the first stage, the proportion between surfactant mixture and lipid phase has been varied to obtain appropriate stable nanocarriers. The optimized NLCs have been further loaded with different amounts of caffeic acid and were analyzed in terms of physical stability, size characteristics, and encapsulation efficiency. The antioxidant activity of CA-loaded NLCs and their release behavior have been tested by specific in vitro methods, e.g., ABTS (2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) assay and release experiments, by Franz cell diffusion. The ABTS assay highlighted a high antioxidant potential of the caffeic acid in association with linseed oil. The capacity to capture ABTS cationic radicals was superior for the NLC entrapping an initial amount of 1.5% CA, the level of antioxidant capacity being 91.3%. The in vitro release experiments showed a different release behavior, depending on the initial amount of caffeic acid used. NLC loaded with a higher concentration of CA manifests a gradual slow release, e.g., 45% CA after 24 h of in vitro experiments, while the NLC loaded with smaller concentration of CA assured a higher release in time, around 65%.
Research on the Prepositive Distance of Crosswalk Warning Markings for Unsignalized Road Section
Authors: Liang Guohua , Wang Fangfang , Shi Quan , Li Rui , Ji Zhijing , Dong Chenchen
Published: February 2021

This paper proposed an optimal prepositive distance of crosswalk warning markings for unsignalized road section under three different design speeds based on the mathematical modelling and driving simulation. To set up the most efficient mathematical modelling for calculating the layout interval of prepositive distance, the vehicles slowing down behaviour characteristics in front of crosswalk were explored. According to the layout interval, the simulation experiment was carried out in the UC-win/Road version 13.0 driving simulator. The rate of speed reduction and the times of maximum deceleration obtained from simulation experiments were selected as evaluation indicators to compare and analyse the deceleration effect related with the prepositive distances of the crosswalk warning markings under three design speeds. The results show that when the design speeds are 30 km/h, 40 km/h, and 50 km/h, the optimal prepositive distances of the crosswalk warning markings are 30 m, 40 m, and 60 m, respectively.
An Ensemble of Adaptive Surrogate Models Based on Local Error Expectations
Authors: Xu Huanwei , Zhang Xin , Li Hao , Xiang Ge
Published: February 2021

An ensemble of surrogate models with high robustness and accuracy can effectively avoid the difficult choice of surrogate model. However, most of the existing ensembles of surrogate models are constructed with static sampling methods. In this paper, we propose an ensemble of adaptive surrogate models by applying adaptive sampling strategy based on expected local errors. In the proposed method, local error expectations of the surrogate models are calculated. Then according to local error expectations, the new sample points are added within the dominating radius of the samples. Constructed by the RBF and Kriging models, the ensemble of adaptive surrogate models is proposed by combining the adaptive sampling strategy. The benchmark test functions and an application problem that deals with driving arm base of palletizing robot show that the proposed method can effectively improve the global and local prediction accuracy of the surrogate model.
Postfailure Characterization of Shallow Landslides Using the Material Point Method
Authors: Nguyen Thanh Son , Yang Kuo-Hsin , Ho Chia-Chun , Huang Feng-Chi
Published: February 2021

Although the mechanisms of slope failure caused by rising groundwater have been widely investigated, the kinematic behavior of landslides in the postfailure stage, which contains essential information for hazard mitigation and risk assessment, has not yet been fully studied. Thus, in this study, a series of numerical simulations using the material point method (MPM) were conducted to analyze the kinematic behavior and soil movement of shallow landslides (infinite slope problems). First, the proposed MPM formulation was validated in a full-scale landslide flume test. The simulated results of final slope profile, runout distance, deposit height, shear band development, slope displacement, and velocity accorded with the experimental results, suggesting that the MPM can quantitatively simulate large deformations. A parametric study of shallow slopes with various hydrological conditions and soil hydraulic and soil mechanical parameters was then performed to assess the influence of the aforementioned factors on landslide kinematics. The simulation results indicated that mechanical behavior at the slope toe is complex; the multiple plastic shear bands generated at the slope toe were due to a combination of shearing and compression. The deposition profile of the slopes was significantly influenced by all input parameters. Among the aforementioned parameters, soil cohesion, location of the groundwater table, and saturated soil permeability most greatly affected runout distance in the sensitivity assessment. Soil friction angle had a minor influence on the kinematic behavior of the slope.
Brachial-Ankle Pulse Wave Velocity as a Novel Modality for Detecting Early Diabetic Nephropathy in Type 2 Diabetes Patients
Authors: Zhang Xueyang , Bai Ran , Zou Linxuan , Zong Junwei , Qin Yang , Wang Yongbo
Published: February 2021

Brachial-ankle pulse wave velocity (baPWV) has been shown to correlate with a host of disorders associated with arterial stiffness. Type 2 diabetes is associated with the involvement of both small vessels and large vessels. Studies on the relevance of baPWV to early diabetic nephropathy are scarce. This retrospective observational case-control study enrolled 120 patients with type 2 diabetes from our medical records. We classified patients into two groups depending on the magnitude of albuminuria: 60 patients with microalbuminuria were classified as the early diabetic nephropathy group (EDN group) and 60 patients without albuminuria were classified as the diabetes without nephropathy group (DWN group). An additional 30 nondiabetic age- and sex-matched controls were also enrolled. Data regarding the lipid profile, blood pressure, baPWV, high-sensitivity C reactive protein (hs-CRP) level, anthropometric measurements, urine albumin/creatinine ratio (UACR), serum creatinine level, and glycemic control indices (i.e., fasting plasma glucose (FPG), postprandial glucose (PPG), and glycosylated hemoglobin (hemoglobin A1c, HbA1c)) were recorded for all enrolled participants. baPWV was significantly higher in the EDN group than in the DWN group. Moreover, baPWV was positively correlated with age, duration of diabetes, obesity, poor glycemic control, and high serum levels of triglycerides (TG), hs-CRP, creatinine, and uric acid as well as a high UACR (all

P
<
0.01

). A significant negative correlation was found between baPWV and high-density lipoprotein levels (

P
<
0.05

). Multivariate regression analysis showed that the hs-CRP level and duration of diabetes most strongly influenced baPWV. baPWV may be a convenient, noninvasive, and reproducible method for detecting early diabetic nephropathy.
LPR‐MLP: A Novel Health Prediction Model for Transmission Lines in Grid Sensor Networks
Authors: Chen Yunliang , Chen Shaoqian , Zhang Nian , Liu Hao , Jing Honglei , Min Geyong
Published: February 2021

The safety of the transmission lines maintains the stable and efficient operation of the smart grid. Therefore, it is very important and highly desirable to diagnose the health status of transmission lines by developing an efficient prediction model in the grid sensor network. However, the traditional methods have limitations caused by the characteristics of high dimensions, multimodality, nonlinearity, and heterogeneity of the data collected by sensors. In this paper, a novel model called LPR‐MLP is proposed to predict the health status of the power grid sensor network. The LPR‐MLP model consists of two parts: (1) local binary pattern (LBP), principal component analysis (PCA), and ReliefF are used to process image data and meteorological and mechanical data and (2) the multilayer perceptron (MLP) method is then applied to build the prediction model. The results obtained from extensive experiments on the real‐world data collected from the online system of China Southern Power Grid demonstrate that this new LPR‐MLP model can achieve higher prediction accuracy and precision of 86.31% and 85.3%, compared with four traditional methods.
Cesarean Section Scar Ectopic Pregnancy in the Second Trimester: An Underrecognized Complication of Cesarean Deliveries
Authors: Holtzman Sharonne , Kiernan Mary Louise , Huntly Jaimie , Kolev Valentin , Zakashansky Konstatin
Published: February 2021

The aim of this paper is to present a case of a cesarean section ectopic pregnancy (CSP) diagnosed in the second trimester and perform a literature review of current guidelines for the management of CSP in the second trimester. This was exempt from the Mount Sinai IRB. This is a case is of a 35-year-old P1122 at 13w4d who presented to our hospital with vaginal spotting and abdominal pain. The patient was found to have a cesarean section ectopic pregnancy with placenta increta. There are no management guidelines for second trimester CSP, and the published material is minimal. A literature review was completed and demonstrated two cases and one case series published on management of existing literature on management of second trimester CSP. Our patient underwent an uncomplicated total laparoscopic hysterectomy with bilateral salpingectomy, bilateral ureterolysis, and cystoscopy. She had an uncomplicated postoperative course and was discharged on postoperative day three with an unremarkable recovery at her two-week postoperative visit.
Performance Analysis and Microbial Community Evolution of In Situ Biological Biogas Upgrading with Increasing H2/CO2 Ratio
Authors: Corbellini Viola , Feng Cuijie , Bellucci Micol , Catenacci Arianna , Stella Tatiana , Espinoza-Tofalos Anna , Malpei Francesca
Published: February 2021

The effect of the amount of hydrogen supplied for the in situ biological biogas upgrading was investigated by monitoring the process and evolution of the microbial community. Two parallel reactors, operated at 37°C for 211 days, were continuously fed with sewage sludge at a constant organic loading rate of 1.5 gCOD∙(L∙d)-1 and hydrogen (H2). The molar ratio of H2/CO2 was progressively increased from 0.5 : 1 to 7 : 1 to convert carbon dioxide (CO2) into biomethane via hydrogenotrophic methanogenesis. Changes in the biogas composition become statistically different above the stoichiometric H2/CO2 ratio (4 : 1). At a H2/CO2 ratio of 7 : 1, the methane content in the biogas reached 90%, without adversely affecting degradation of the organic matter. The possibility of selecting, adapting, and enriching the original biomass with target-oriented microorganisms able to biologically convert CO2 into methane was verified: high throughput sequencing of 16S rRNA gene revealed that hydrogenotrophic methanogens, belonging to Methanolinea and Methanobacterium genera, were dominant. Based on the outcomes of this study, further optimization and engineering of this process is feasible and needed as a means to boost energy recovery from sludge treatment.
Assessment of Applying Global Instruments in Nongovernmental Organizations for Environmental Security and Sustainable Development in Developing Countries
Authors: Zikargae Mekonnen Hailemariam
Published: February 2021

Background. Environmental challenges are overwhelming the global communities. Thus, the purpose of the study is to explore how instruments used by the nongovernmental organizations are applied for environmental security and sustainable development in Ethiopia. It addresses issues of how environmental education in context is working to instill the knowledge, skills, awareness, and attitudes of the stakeholders. Recent discussions of the African Union Summit 2020, Africa Agenda 2063, Davos 2020 World Economic Forum, United Nations Agenda 2030, and the Green Economy Strategy in Ethiopia have strongly sought to strengthen environmental education as an instrument of global and local sustainability of the environment and development. Here, the study collected pieces of evidence from environmental programs of a nongovernmental organization in Ethiopia. The study focused on a nonformal environmental education, based on the frameworks of the agreements and declarations where Ethiopia is a contracting party. The frameworks are guiding concepts to investigate the phenomenon. Methods. The study used a thematic analysis based on empirical studies. Specifically, empirical studies from primary and secondary sources on the implementation of environment and forest development programs of the organization are crucial to providing a concrete presentation. Results. Empirical pieces of evidence show that the organization plans, projects, and performance reports were found inconsistent with the frameworks of international agreements and national policy. The empirical study also shows that environmental education is not well considered and institutionalized in the organization's project planning. Environmental education strategies are not explicitly visible while planning the projects. Moreover, in some implementation strategies of the organization, there was inconsistency in using environmental education as a strategic instrument to improve environmental security and quality. Conclusion. The organization's environmental performance was deep-rooted to improve the status quo in the living community. However, the utilization of environmental education was discovered to be minimal. Thus, stakeholders and the organization take the advice to integrate into the entire cycle of the project.
Safety and Clinical Activity of Atezolizumab in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase I Study
Authors: Petrylak Daniel P. , Loriot Yohann , Shaffer David R. , Braiteh Fadi , Powderly John , Harshman Lauren C. , Conkling Paul , Delord Jean-Pierre , Gordon Michael , Kim Joseph W. , Sarkar Indrani , Yuen Kobe , Kadel Edward E. , Mariathasan Sanjeev , O'Hear Carol , Narayanan Sujata , Fassò Marcella , Carroll Susheela , Powles Thomas
Published: February 2021

Purpose:

Atezolizumab [anti–programmed death-ligand 1 (anti-PD-L1)] is well tolerated and efficacious in multiple cancers, but has not been previously evaluated in metastatic castration-resistant prostate cancer (mCRPC). This study examined the safety, efficacy, and biomarkers of atezolizumab monotherapy for mCRPC.

Patients and Methods:

This phase Ia, open-label, dose-escalation and dose-expansion study (PCD4989g) enrolled patients with mCRPC who had progressed on sipuleucel-T or enzalutamide. Atezolizumab was given intravenously every 3 weeks until confirmed disease progression or loss of clinical benefit. Prespecified endpoints included safety, efficacy, biomarker analyses, and radiographic assessments.

Results:

All 35 evaluable patients [median age, 68 years (range, 45–83 years)] received atezolizumab after ≥1 prior line of therapy; 62.9% of patients had received ≥3 prior lines. Treatment-related adverse events occurred in 21 patients (60.0%), with no deaths. One patient had a confirmed partial response (PR) per RECIST 1.1, and 1 patient had a PR per immune-related response criteria. The confirmed 50% PSA response rate was 8.6% (3 patients). Median overall survival (OS) was 14.7 months [95% confidence interval (CI): 5.9–not evaluable], with a 1-year OS rate of 52.3% (95% CI: 34–70); 2-year OS was 35.9% (95% CI: 13–59). Median follow-up was 13.0 months (range, 1.2–28.1 months). Biomarker analyses showed that atezolizumab activated immune responses; however, a composite biomarker failed to reveal consistent correlations with efficacy.

Conclusions:

Atezolizumab was generally well tolerated in patients with mCRPC, with a safety profile consistent with other tumor types. In heavily pretreated patients, atezolizumab monotherapy demonstrated evidence of disease control; however, its limited efficacy suggests a combination approach may be needed.
Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy forGNAQ-Driven Uveal Melanoma
Authors: Paradis Justine S. , Acosta Monica , Saddawi-Konefka Robert , Kishore Ayush , Lubrano Simone , Gomes Frederico , Arang Nadia , Tiago Manoela , Coma Silvia , Wu Xingyu , Ford Kyle , Day Chi-Ping , Merlino Glenn , Mali Prashant , Pachter Jonathan A. , Sato Takami , Aplin Andrew E. , Gutkind J. Silvio
Published: February 2021

Purpose:

Uveal melanoma is the most common eye cancer in adults. Approximately 50% of patients with uveal melanoma develop metastatic uveal melanoma (mUM) in the liver, even after successful treatment of the primary lesions. mUM is refractory to current chemo- and immune-therapies, and most mUM patients die within a year. Uveal melanoma is characterized by gain-of-function mutations in GNAQ/GNA11, encoding Gαq proteins. We have recently shown that the Gαq–oncogenic signaling circuitry involves a noncanonical pathway distinct from the classical activation of PLCβ and MEK–ERK. GNAQ promotes the activation of YAP1, a key oncogenic driver, through focal adhesion kinase (FAK), thereby identifying FAK as a druggable signaling hub downstream from GNAQ. However, targeted therapies often activate compensatory resistance mechanisms leading to cancer relapse and treatment failure.

Experimental Design:

We performed a kinome-wide CRISPR-Cas9 sgRNA screen to identify synthetic lethal gene interactions that can be exploited therapeutically. Candidate adaptive resistance mechanisms were investigated by cotargeting strategies in uveal melanoma and mUM in vitro and in vivo experimental systems.

Results:

sgRNAs targeting the PKC and MEK–ERK signaling pathways were significantly depleted after FAK inhibition, with ERK activation representing a predominant resistance mechanism. Pharmacologic inhibition of MEK and FAK showed remarkable synergistic growth-inhibitory effects in uveal melanoma cells and exerted cytotoxic effects, leading to tumor collapse in uveal melanoma xenograft and liver mUM models in vivo.

Conclusions:

Coupling the unique genetic landscape of uveal melanoma with the power of unbiased genetic screens, our studies reveal that FAK and MEK–ERK cotargeting may provide a new network-based precision therapeutic strategy for mUM treatment.

See related commentary by Harbour, p. 2967
Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912)
Authors: Foster Jennifer H. , Voss Stephan D. , Hall David C. , Minard Charles G. , Balis Frank M. , Wilner Keith , Berg Stacey L. , Fox Elizabeth , Adamson Peter C. , Blaney Susan M. , Weigel Brenda J. , Mossé Yael P.
Published: February 2021

Purpose:

Anaplastic lymphoma kinase (ALK) aberrations are a promising target for patients with neuroblastoma. We assessed the activity of first-generation ALK inhibitor crizotinib in patients with no known curative treatments and whose tumors harbored an activating ALK alteration.

Patients and Methods:

Twenty patients with relapsed/refractory ALK-positive neuroblastoma received crizotinib at the recommended phase II dose of 280 mg/m2/dose. A Simon two-stage design was used to evaluate the antitumor activity of crizotinib monotherapy. Response evaluation occurred after cycles 1, 3, 5, 7, and then every 3 cycles. Correlation of ALK status and response was a secondary aim of the study.

Results:

The objective response rate for patients with neuroblastoma was 15% [95% confidence interval (CI): 3.3%–34.3%]: two with partial responses and 1 with a complete response. All three patients had a somatic ALK Arg1275Gln mutation, the most common ALK hotspot mutation observed in neuroblastoma and the only mutation predicted to be sensitive to ALK inhibition with crizotinib. Two patients had prolonged stable disease (10 and 13 cycles, respectively); both harbored an ALK Arg1275Gln mutation. Three patients with ALK Phe1174Leu mutations progressed during cycle 1 of therapy, and one patient with an ALK Phe1174Val received three cycles before disease progression. The two patients with ALK amplification had no response. The most common adverse event was a decrease in neutrophil count.

Conclusions:

Despite limited activity seen in this trial, we conclude that this is more likely due to an inability to reach the higher concentrations of crizotinib needed to overcome the competing ATP affinity.

See related commentary by Schulte and Eggert, p. 3507
Recent Understanding of Peritoneal Pathology in Peritoneal Dialysis Patients in Japan
Authors: Hamada Chieko , Tomino Yasuhiko
Published: February 2021

The thin peritoneum covering the peritoneal cavity has been used as a dialysis membrane for peritoneal dialysis (PD) because it is highly vascularized and has a large body surface area. However, it has been reported that peritoneal membranes affected by peritonitis, as well as those exposed to the nonphysiological high glucose levels containing PD dialysate, may undergo histological and functional changes. Patients undergoing PD may experience encapsulating peritoneal sclerosis (EPS), which is a life-threatening serious complication of PD that can significantly impair activities of daily living. The incidence of EPS was 1.4–7.3% of maintenance PD patients in the 1980s. The incidence has improved to 1.0% after a neutral dialysate became the standard PD treatment in Japan. Furthermore, the pathogenesis of EPS is uncertain although its onset may be explained by the “two-hit theory,” in which some factors leading to impairment had an additive effect on simple peritoneal sclerosis. The evaluation of histopathological findings has shown the impact of the neutral dialysate on peritoneal deterioration as well as its role in the development of functional changes. In the present report, we discuss the advances in the understanding of peritoneal deterioration based on histological and macroscopic evaluations of the peritoneum of patients undergoing PD. We also discuss the recent treatment for PD patients.
Characterization of Traumatic Brain Injury Research in the Middle East and North Africa Region: A Systematic Review
Authors: Al-Hajj Samar , Hammoud Zeinab , Colnaric Jure , Ataya Maya , Macaron Marie Michele , Kadi Kamil , Harati Hayat , Phipps Helen , Mondello Stefania , Tamim Hani , Abou Abbass Hussein , Kobeissy Firas ,   the TBI Working Group
Published: February 2021

Objectives: Traumatic brain injury (TBI) represents a major health concern worldwide with a large impact in the Middle East and North Africa (MENA) region as a consequence of protracted wars and conflicts that adversely affect the general population. Currently, systematic TBI studies in the MENA region are lacking, nonetheless they are immensely needed to enhance trauma management and increase survival rates among TBI patients. This systematic review aims to characterize TBI in the MENA region to guide future policy choices and research efforts and inform tailored guidelines capable of improving TBI management and patient treatment and outcome. Furthermore, it will serve as a road map to evaluate and assess knowledge of trauma impact on regional health systems that can be adopted by health-care providers to raise awareness and improve trauma care. Methods: We conducted a comprehensive search strategy of several databases including MEDLINE/Ovid, PubMed, Embase, Scopus, CINAHL, Google Scholar, and the grey literature in accordance with the PROSPERO systematic review protocol CRD42017058952. Abstracts were screened, and selected eligible studies were reviewed independently by 2 reviewers. We collected demographics information along with TBI characteristics, mortality rates, and regional distribution. Data were extracted using REDCap and checked for accuracy. Results: The search strategy yielded 23,385 citations; 147 studies met the eligibility criteria and were included in this review. Motor vehicle accident (MVA) was the leading cause of TBI (41%) in the MENA region, followed by the military- (15.6%) and fall- (8.8%) related TBI. Males predominantly suffer from TBI-related injuries (85%), with a high prevalence of MVA- and military-related TBI injuries. The TBI mortality rate was 12.9%. The leading causes of mortality were MVA (68%), military (20.5%), and assault (2.9%). The vast majority of reported TBI severity was mild (63.1%) compared to moderate (10.7%) and severe TBI (20.2%). Patients mainly underwent a Glasgow Coma Scale assessment (22.1%), followed by computed tomography scan (8.9%) and surgery (4.1%). Conclusions: Despite its clinical, social, and economic burden, the evidence of TBI research in the MENA region is scarce. Further research and high-quality epidemiological studies are urgently needed to gain a deep understanding of the TBI burden in the region, facilitate the allocation of adequate resources, implement effective preventive and intervention strategies and advise on the TBI patient management as reflective on the TBI patterns and modes.
Modified Laparoscopic and Robotic Flap Pyeloplasty for Recurrent Ureteropelvic Junction Obstruction with a Long Proximal Ureteral Stricture: The “Wishbone” Anastomosis and the “Ureteral Plate” Technique
Authors: Cheng Sida , Li Xinfei , Yang Kunlin , Xiong Shengwei , Li Ziao , Zhu Hongjian , Zhang Peng , Li Xuechao , Guan Hua , Li Zhihua , Hao Han , Zhang Lei , Li Xuesong , Zhou Liqun
Published: February 2021

Objectives: The aim of the study was to present our modified flap pyeloplasty techniques for recurrent ureteropelvic junction obstruction (UPJO) with a long proximal ureteral stricture and compare outcomes of laparoscopic and robotic procedures. Materials and Methods: Between March 2018 and January 2020, 21 patients underwent modified laparoscopic or robotic flap pyeloplasty for recurrent UPJO with a long proximal ureteral stricture. Our surgical modifications included the “wishbone” anastomosis and “ureteral plate” technique. Demographic, perioperative, and follow-up data were recorded and compared retrospectively between the groups. Success was defined as subjective pain alleviation and hydronephrosis improvement. Results: Thirteen modified laparoscopic flap pyeloplasty (mLFP) and 8 modified robotic flap pyeloplasty (mRFP) were performed successfully without conversion. mRFP tended to have shorter overall operative time (142.4 vs. 179.1 min, p = 0.122) and anastomosis time (43.1 vs. 61.0 min, p = 0.093) than mLFP. No difference was found in estimated blood loss (p = 0.723) and pararenal draining time (p = 0.175) between the groups. The mean postoperative hospital stay of mRFP was significantly shorter than that of mLFP (5.0 vs. 8.2 days, p = 0.015). No major complications occurred. During the mean follow-up of 17.9 months, the overall success rate was 90.5%, and there was no significant difference between 2 groups. Conclusions: The modified flap pyeloplasty could be considered a practical and effective treatment option with a high success rate for recurrent UPJO with a long proximal ureteral stricture, and the robotic procedures showed advantages of higher efficiency and faster recovery.
Teledermatology in Times of COVID-19 Confinement: Comparing Patients’ and Physicians’ Satisfaction by the Standardized Brest Teledermatology Questionnaire
Authors: Fluhr Joachim W. , Gueguen Annie , Legoupil Delphine , Brenaut Emilie , Abasq Claire , Araújo Helena , Misery Laurent
Published: February 2021

The French government imposed the first COVID-19 pandemic lockdown from March 17 until May 11, 2020. Only emergency cases and teledermatology (TD) were allowed in outpatient settings. A standardized questionnaire was developed to compare the satisfaction level of patients and their treating physicians. Our main question was whether the patients would perceive TD as a valid alternative for direct physical face-to-face consultation. Eighty-two patients and their 4 treating dermatologists from one dermatology department participated in the study (43 females, 39 males) with a mean age of 46.6 years (SD ±23.9). The reason for TD was a chronic disease in the majority (87.8%), and mainly as a follow-up (96.3%). Regarding satisfaction, almost all categories rated around 9 on a 0–10 verbal analogue scale. The same level of global satisfaction could be seen between the patients and the physicians as well as for the quality of the patient-physician relation and whether all questions could be addressed during the TC. Physicians showed significantly higher scores than patients only for the category of “length” of the consultation. Gender, age, as well as distance between the clinic and home of the patient were not influencing factors for satisfaction. Regarding the technical parameters, the evaluation was mostly comparable for patients and physicians, but overall lower than the relational satisfaction parameters, especially for image quality. Patients were significantly more motivated to continue the TD after the lockdown than their treating dermatologists. We see an interest for implementing TD in specialized centers with chronic patients coming from remote places for regular follow-ups. TD cannot replace in-person patient-physician interaction, but was helpful during the lockdown. As a result, TD might become part of dermatology training to prepare for future lockdown situations.
The Deep Roots of Addiction: A Comparative Perspective
Authors: Karnib Nabil , van Staaden Moira J.
Published: February 2021

Addiction is a debilitating condition that extracts enormous social and economic tolls. Despite several decades of research, our knowledge of its etiology, preventive measures, and treatments is limited. A relatively recent research field with the potential to provide a more holistic understanding, and subsequently treatments, takes a phylogenetic view of addiction. This perspective is based on deep homologies at the genetic, proteomic, and behavioral levels, which are shared across all metazoan life; particularly those organisms faced with plant secondary metabolites as defensive compounds against insect herbivory. These addictive alkaloids, such as nicotine, cocaine, or cathinone, are commonly referred to as “human drugs of abuse” even though humans had little to no role in the co-evolutionary processes that determined their initial emergence or continued selection. This commentary discusses the overwhelming homologies of addictive alkaloid effects on neural systems across a wide range of taxa, as we aim to develop a broader comparative view of the “addicted brain.” Taking nicotine as an example, homologous physiological responses to this compound identify common underlying cellular and molecular mechanisms that advocate for the adoption of a phylogenetic view of addiction.
Mobile Robot Localization: A Review of Probabilistic Map-Based Techniques
Authors: Malagon-Soldara Salvador Manuel , Toledano-Ayala Manuel , Soto-Zarazua Genaro , Carrillo-Serrano Roberto Valentin , Rivas-Araiza Edgar Alejandro
Published: February 2021

This work presents a comprehensive review of current probabilistic developments used to calculate position by mobile robots in indoor environments. In this calculation, best known as localization, it is necessary to develop most of the tasks delegated to the mobile robot. It is then crucial that the methods used for position calculations be as precise as possible, and accurately represent the location of the robot within a given environment. The research community has devoted a considerable amount of time to provide solutions for the localization problem. Several methodologies have been proposed the most common of which are based in the Bayes rule. Other methodologies include the Kalman filter and the Monte Carlo localization filter wich will be addressed in next sections. The major contribution of this review rests in offering a wide array of techniques that researchers can choose. Therefore, method-sensor combinations and their main advantages are displayed.