bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Levels of Matrix Metalloproteinase-1 in Brazilian Patients with Benign Prostatic Hyperplasia or Prostate Cancer
Authors: El-Chaer William Khalil , Tonet-Furioso Audrey Cecília , Morais Junior Gilberto Santos , Souza Vinícius Carolino , Avelar Gleiciane Gontijo , Henriques Adriane Dallanora , Franco Moraes Clayton , Nóbrega Otávio Toledo
Published: May 2020

Metalloproteinases (MMPs) are involved in metastatic tumor processes, with changes in circulating levels detected in several cancer types. Here, we compare serum concentrations of metalloproteinase-1 (MMP-1) across individuals clinically diagnosed with prostate cancer (PCa) or benign prostatic hyperplasia (BPH), correcting results for the rs495366 single nucleotide polymorphism (SNP) that predisposes to differential MMP-1 levels. 196 men aged ≥50 years were followed at a university hospital urology outpatient clinic, with clinical, anthropometric, and rectal examinations performed by one urologist. Blood samples obtained prior to any clinical intervention provided baseline MMP-1 and total/free PSA levels as well as metabolic, hormonal, and inflammatory markers. The SNP was genotyped by real-time PCR. Participants with medical and/or laboratory profile compatible with malignancy composed the PCa group when confirmed by the Gleason scale. As expected, A-allele homozygotes showed reduced levels of MMP-1. Genotype-adjusted analyses revealed the mean MMP-1 level as 2-fold higher in PCa carriers compared to BPH patients. No other differences were found according to the prostatic condition or genotypic distribution, except for the expected raise in total and free PSA levels in PCa. In conclusion, increased serum levels of MMP-1 were observed in this context of prostatic malignancy compared to a benign phenotype, regardless of a genetic influence.
Th9 Cells in Peripheral Blood Increased in Patients with Immune-Related Pancytopenia
Authors: Shao Qing , Wang Yangyang , Liu Zhaoyun , Liu Hui , Wang Yihao , Zhao Yang , Li Lijuan , Fu Rong
Published: May 2020

Background. Immune-related pancytopenia (IRP) is a kind of autoimmune disease mediated by autoantibodies in bone marrow. T helper 9 (Th9) cell is a new subset of T cell discovered recently, which mainly expresses cytokine interleukin-9 (IL-9) to exert immune function. Th9 cells are associated with a variety of inflammatory diseases, but the role of Th9 cells in IRP remains unclear. Methods. Fifty patients with IRP and 20 healthy controls were enrolled. The percentage of Th9 cells was detected by flow cytometry (FCM) and ELISA. CD4+ lymphocytes were sorted by magnetic beads, and the mRNA expression levels of Th9 cells related transcription factors PU.1 and BATF were detected by RT-PCR. Results. The percentage of Th9 cells in CD3+CD4+ cells was 2.73±1.96% in the untreated group, which was significantly higher than those in the remission group (1.21±0.86%) (p<0.01) and the control group (0.68±0.40%) (p<0.001). And that in the remission group was significantly higher than that in the control group (p<0.05). The level of IL-9 in the untreated group was 183.91±112.42 pg/mL, which was significantly higher than that in the remission group (105.96±64.79 pg/mL) (p<0.01) and control group (56.03±14.49 pg/mL) (p<0.001). That in the remission group was also significantly higher than that in the control group (p<0.01). They were negatively correlated with hemoglobin, red blood cell, white blood cell, and platelet counts and positively correlated with the percentage of CD19+B cells and CD5+CD19+/CD19+B cells, respectively. The mRNA expression levels of PU.1 and BATF in IRP patients were higher than those in controls (p<0.05). Conclusions. The percentage of Th9 cells in the peripheral blood and the level of IL-9 in the serum of patients with IRP were increased, which was related to the severity of the disease.
Neuromuscular, Perceptual, and Temporal Determinants of Movement Patterns in Wheelchair Fencing: Preliminary Study
Authors: Borysiuk Zbigniew , Nowicki Tadeusz , Piechota Katarzyna , Błaszczyszyn Monika
Published: May 2020

The objective of the present study was to determine the structure of the movement pattern performed during a wheelchair fencing lunge that is executed in response to visual and sensory stimuli. In addition, a comparison was made between fencers in the categories A and B of disability. In addition, the analysis involved the correlation between the duration of the sensorimotor response and the value of the bioelectric signal recorded in selected muscles. Seven Paralympic team athletes specializing in wheelchair fencing (3 in category A and 4 in category B) participated in the research. The fencers perform at international level competitions and are multiple medalists of the Paralympic Games. In the study, a wireless system for sEMG and accelerometer signal measurement was employed to test the intervals between the initiation of the lunge attack and its termination defined by the touch of the weapon on the coach’s torso. The electrodes were placed on 9 key muscles responsible for the effectiveness of the executed attack: DEL, TRI, BC, ECR FCR, LD, and EAO. The significant intergroup difference in the muscle activation was found to be 0.333 s for category A fencers and 0.522 s for category A fencers at p = 0.039 applies to the latissimus dorsi (LD LT) muscle, which demonstrates its significance as a postural muscle in the structure of the examined movement pattern. In terms of the values of EMG, a tendency for higher MVC (%) values in most muscles for category A competitors was recorded. The latissimus dorsi (DL RT) muscle with an intergroup difference of MVC‐114.63 for cat. A and 67.50 for cat. B at p = 0.039 turned out to play a significant role. The results prove the role of postural muscles: external abdominal oblique and latissimus dorsi on the effectiveness of the attacks executed in wheelchair fencing.
Preoperative Steroid Use in Rhegmatogenous Retinal Detachment Associated with Choroidal Detachment after 23-Gauge Vitrectomy
Authors: Wu Jianhua , Zhang Rui , He Junwen , Xu Changzhong , Li Zhaohui
Published: May 2020

Background. Rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) is rare and the prognosis is poor. This retrospective study evaluated the effect of preoperative steroid on the clinical outcome of patients with RRDCD receiving 23-gauge pars plana vitrectomy (PPV). Methods. Sixty-six patients (67 eyes) with diagnosed RRDCD underwent 23-gauge PPV. The patients assigned to receive systemic or subtenon injection of preoperative steroids were considered Group A (35 eyes) and did not receive are considered Control Group B (32 eyes). Most patients in Group A received subtenon injection of glucocorticoids. The cyclodialysis angle was measured with ultrasound biomicroscopy. Preoperative, intraoperative, and postoperative data were compared. Results. The rates of retinal reattachment in Group A after the first and second operations were 68.8% (24/35 eyes) and 91.43% (32/35 eyes), respectively, which were not significantly different from that of Group B (78.1%, 25/32 eyes; 96.6%, 31/32 eyes). The logMAR (logarithm of the minimum angle of resolution) visual acuity in Group A (1.63 ± 0.75) was similar to that of Group B (1.34 ± 0.74). Postoperative intraocular pressure and ocular hypertension in Group A (17.94 ± 9.82 mmHg and 37.1%, respectively; 13/35 eyes) were comparable to that of Group B (20.93 ± 10.21 mmHg and 56.3%; 18/32 eyes). Logistic regression analysis showed that postoperative reattachment was negatively associated with preoperative cyclodialysis angle as measured with ultrasound biomicroscopy (P=0.048) but was not significantly associated with preoperative steroid use (P=0.907). Conclusions. Preoperative steroid use does not improve retinal reattachment and visual acuity in patients with RRDCD after 23-gauge PPV. Preoperative measurement of the cyclodialysis angle with ultrasound biomicroscopy may be useful for predicting clinical outcomes.
The Analysis on Seepage Field of Grouted and Shotcrete Lined Underwater Tunnel
Authors: Qin Zhenggui , Wang Yuan , Song Yi , Dong Qi
Published: May 2020

Groundwater control in underwater tunnels by drilling and blasting method is generally carried out by grouting ring, shotcrete lining (primary lining), and concrete lining. The permeable grouting ring and shotcrete lining have an important impact on seepage field. However, the currently published research models of related results are for homogeneous and isotropic single-layer unlined tunnels, ignoring the important effects of tunnel grouting circles and primary lining. If the conclusions of the relevant literature are directly used to guide the tunnel design, large errors may occur. Therefore, on the basis of previous studies, this article extends the tunnel seepage research model and incorporates the tunnel grouting ring and primary lining into the research model. The research model is more in line with actual working conditions. Based on the principle of mirror method, the seepage field of a drainage tunnel in an infinite aquifer is superposed with that of a water supply tunnel in an infinite aquifer, and the analytical solution to the seepage field of an grouted and shotcrete lined underwater tunnel in a semi-infinite aquifer is obtained, which is further verified by numerical analysis and experiment. In addition, the influence of grouting ring and primary lining parameters on seepage field is discussed by using partial differential analysis. The results show that the seepage flow of tunnel can be significantly alleviated by either reducing the permeability coefficient of grouting ring and primary lining or increasing the thickness of grouting ring and primary lining, but the water pressure of grouting ring and primary lining will increase.
Exploring the Potential Use of Hylocereus polyrhizus Peels as a Source of Cosmeceutical Sunscreen Agent for Its Antioxidant and Photoprotective Properties
Authors: Vijayakumar Ramya , Abd Gani Siti Salwa , Zaidan Uswatun Hasanah , Halmi Mohd Izuan Effendi , Karunakaran Thiruventhan , Hamdan Mohd Razak
Published: May 2020

Currently, consumers’ demand for sunscreens derived from natural sources that provide photoprotection from ultraviolet (UV) radiation is pushing the cosmetic industry to develop breakthrough formulations of sun protection products by incorporating plant antioxidants as their active ingredients. In this context, the present study was initiated to evaluate the antioxidant and photoprotective properties of the underutilized Hylocereus polyrhizus peel extract (HPPE) using in vitro spectrophotometric techniques. The phytochemical screenings of HPPE conducted via high‐performance liquid chromatography (HPLC) and ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UPLC‐QTOF/MS) revealed the presence of phenolic acids and flavonoids as the major secondary metabolites in HPPE. The antioxidant potentials evaluated based on 2, 2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) radical and total antioxidant capacity assays were in the range of 22.16 ± 0.24%–84.67 ± 0.03% with 50% inhibitory concentration (IC50) of 36.39 ± 0.04 μg/mL and 23.76 ± 0.14%–31.87 ± 0.26% (IC50 = 21.93 ± 0.07 μg/mL), respectively. For the photoprotective evaluation, the results showed that HPPE had significantly high absorbance values (3.1–3.6) at 290–320 nm with an exceptional sun protection factor (SPF) value of 35.02 ± 0.39 at 1.00 mg/mL. HPPE also possessed a broad‐spectrum shielding power against both UVA and UVB radiations. Hence, in terms of practical implications, our findings would offer an exciting avenue to develop a photoprotective formulation incorporating the ethanolic extract of Hylocereus polyrhizus peels as a synergistic active ingredient for its excellent UV absorption properties and the strong antioxidant activities.
The Effect of Different Treatment Regimens and Multiple Risk Factors on Adverse Pregnancy Outcomes among Syphilis‐Seropositive Women in Guangzhou: A Retrospective Cohort Study
Authors: Hu Fang , Guo Shuai-Jun , Lu Jian-Jun , Zhu Sui , Hua Ning-Xuan , Song Yan-Yan , Liang Jing-Jing , Yu Jia , Lin Sui-Fang
Published: May 2020

Background. To eliminate mother‐to‐child transmission of syphilis, the Chinese government recommends a treatment regimen that slightly differs from the World Health Organization‐ (WHO‐) recommended treatment. However, little is known about their difference in efficacy. This study is aimed at comparing the effect of China‐recommended and WHO‐recommend treatment regimens on adverse pregnancy outcomes (APOs) and at examining associated risk factors of APOs among syphilis‐seropositive women. Methods. Using the syphilis registry data, we retrospectively collected data from 4488 syphilis‐infected pregnant women in Guangzhou during 2011‐2018. Multivariate analyses were used to investigate the association between treatment regimens and APOs (ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth or low birth weight, newborn smaller than gestational age, congenital syphilis, and infant death) and the association between risk factors and APOs. Results. Of 3474 participants, 27.3% had at least one APO. Compared to those receiving WHO‐recommended treatment, women who received China‐recommended treatment were less likely to have APOs (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.38‐0.57), whereas those who received no treatment had 1.6 times higher odds of experiencing APOs. One common risk factor across different APOs was high levels of log2‐transformed toluidine red unheated serum test (TRUST) titers before treatment (OR 1.14, 95% CI 1.10‐1.19). China‐recommended treatment was effective in reducing APOs for those with TRUST ≥ 1 : 8 (OR 0.21, 95% CI 0.14‐0.29) and those with TRUST < 1 : 8 (OR 0.62, 95% CI 0.50‐0.77). Conclusions. Syphilis‐seropositive women receiving China‐recommended treatment had lower odds of APOs, especially when TRUST titers before treatment were high. Findings can be used to guide health professionals to reduce APOs among syphilis‐infected mothers and promote nationwide use of China‐recommended treatment.
Analysis of Lumbar Sagittal Curvature in Spinal Decompression and Fusion for Lumbar Spinal Stenosis Patients under Roussouly Classification
Authors: Zhang Guoqiang , Yang Yong , Hai Yong , Li Jinjun , Xie Xuehu , Feng Shitong
Published: May 2020

To evaluate the clinical significance of spinal decompression and fusion for lumbar spinal stenosis in old patients under Roussouly classification, 160 old patients (>60 year old) with lumbar spinal stenosis underwent spinal decompression, and fusion were retrospectively studied. According to Roussouly classification, patients were divided into 4 groups, in which Roussouly types I, II, and IV were the nonstandard group and Roussouly type III was the standard group. Visual analog scale (waist, leg) and Oswestry disability index (ODI) scores were recorded before operation and at the final follow‐up. All patients improved the sagittal curvature: for patients in Roussouly types I and II, there were statistically significant differences in terms of postoperative global lordosis (GL), global kyphosis (GK), sacral slope (SS), sagittal vertical axis (SVA), and pelvic tilt (PT) compared with that before surgery (all P < 0.001); patients in Roussouly type IV obtained similar results with type III after surgery. The four groups showed significant improvement in ODI and VAS scores at final follow‐up (all P < 0.001). After regrouping at the final follow‐up, the proportion of the standard type (Roussouly type III) patients was increased compared with preoperative. In conclusion, Roussouly classification has important guiding significance in spinal decompression and fusion for old patients (>60 years) with lumbar spinal stenosis.
Fusion of FDG-PET Image and Clinical Features for Prediction of Lung Metastasis in Soft Tissue Sarcomas
Authors: Deng Jin , Zeng Weiming , Shi Yuhu , Kong Wei , Guo Shunjie
Published: May 2020

Extracting massive features from images to quantify tumors provides a new insight to solve the problem that tumor heterogeneity is difficult to assess quantitatively. However, quantification of tumors by single-mode methods often has defects such as difficulty in features extraction and high computational complexity. The multimodal approach has shown effective application prospects in solving these problems. In this paper, we propose a feature fusion method based on positron emission tomography (PET) images and clinical information, which is used to obtain features for lung metastasis prediction of soft tissue sarcomas (STSs). Random forest method was adopted to select effective features by eliminating irrelevant or redundant features, and then they were used for the prediction of the lung metastasis combined with back propagation (BP) neural network. The results show that the prediction ability of the proposed model using fusion features is better than that of the model using an image or clinical feature alone. Furthermore, a good performance can be obtained using 3 standard uptake value (SUV) features of PET image and 7 clinical features, and its average accuracy, sensitivity, and specificity on all the sets can reach 92%, 91%, and 92%, respectively. Therefore, the fusing features have the potential to predict lung metastasis for STSs.
TNFα Mediates the Interaction of Telomeres and Mitochondria Induced by Hyperglycemia: A Rural Community-Based Cross-Sectional Study
Authors: Lyu Lu , He Shuli , Zhang Huabing , Li Wei , Zeng Jingbo , Ping Fan , Li Yu-Xiu
Published: May 2020

This study is aimed at evaluating the relationship between leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) in a noninterventional rural community of China with different glucose tolerance statuses. In addition, we investigate whether the indicators of oxidative stress and inflammation were involved and identify mediators among them. A total of 450 subjects in rural China were included and divided into two groups according to a 75 g oral glucose tolerance test (OGTT): the abnormal glucose metabolism (AGM, n=257, 57.1%) group and the normal glucose tolerance (NGT, n=193, 42.9%) group. Indicators of oxidative stress (superoxide dismutase (SOD) and glutathione reductase (GR)) and inflammatory indices (tumor necrosis factor α (TNFα) and interleukin-6 (IL-6)) were all determined by ELISA. LTL and mtDNAcn were measured using a real-time PCR assay. Linear regressions were used to adjust for covariates that might affect the relationship between LTL and mtDNAcn. Mediation analyses were utilized to evaluate the mediators. In the AGM, LTL was correlated with mtDNAcn (r=0.214, p=0.001), but no correlation was found in the NGT. The association between LTL and mtDNAcn was weakened after adjusting for inflammatory factors in the AGM (p=0.087). LTL and mtDNAcn were both inversely related to HbA1c, IL-6, TNFα, and SOD activity. Mediation analysis demonstrated that TNFα was a significant mediator in the telomere-mitochondrial interactome in the AGM. This result suggests that inflammation and oxidative stress may play a vital role in telomere shortening as well as mitochondrial dysfunction. In the subjects with hyperglycemia, a significant positive correlation is observed between LTL and mtDNAcn, which is probably mediated by TNFα. TNFα may be considered a potential therapeutic target against aging-related disease in hyperglycemia.
On the Ground State to Hamiltonian Elliptic System with Choquard’s Nonlinear Term
Authors: Wang Wenbo , Zhou Jianwen , Li Yongkun
Published: May 2020

In the present paper, we consider the following Hamiltonian elliptic system with Choquard’s nonlinear term −Δu+Vxu=∫ΩGvy/x−yβdygv in Ω,−Δv+Vxv=∫ΩFuy/x−yαdyfu in Ω,u=0,v=0 on ∂Ω,where Ω⊂ℝN is a bounded domain with a smooth boundary, 0<α<N, 0<β<N, and F is the primitive of f, similarly for G. By establishing a strongly indefinite variational setting, we prove that the above problem has a ground state solution.
Dracocephalum moldavica L. Extracts Protect H9c2 Cardiomyocytes against H2O2‐Induced Apoptosis and Oxidative Stress
Authors: Jin Min , Yu Hui , Jin Xia , Yan Lailai , Wang Jingyu , Wang Zhanli
Published: May 2020

Background and Objectives. Dracocephalum moldavica L. is an herbal medicine used to treat cardiovascular diseases in China. The purpose of this study was to assess the cardioprotective effect of D. moldavica L. extracts against H2O2‐induced apoptosis and oxidative stress in H9c2 cells and to explore the mechanism behind this effect. Materials and Methods. The petroleum ether (petrol), dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n‐butyl alcohol (n‐BuOH) fractions were isolated from alcohol extracts of D. moldavica L. Total phenolic and flavonoid contents and in vitro antioxidant activities of different fractions were evaluated. H9c2 cells were then treated with D. moldavica L. extracts before challenging with H2O2. Cell viability was determined by colorimetric assay, and ELISA was used to measure the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD). Apoptosis levels and mitochondrial membrane potential were measured by flow cytometry. The expressions of cell apoptosis regulatory proteins caspase‐3, Bax, and Bcl‐2 were determined by western blotting. Results. Our results demonstrated that the EtOAc fraction from D. moldavica L. ethanol extract, which is rich in phenolic and flavonoid active constituents, had the strongest free radical scavenging activity. Additionally, this fraction increased H2O2‐induced reduction in cell viability, SOD activity, and mitochondrial membrane potential. It also reduced H2O2‐induced elevation in ROS production, contents of LDH and MDA, and H9c2 apoptosis. We further found that the EtOAc fraction increased Bcl‐2 expression, while it decreased caspase‐3 and Bax expressions induced by H2O2 in H9c2 cells. Conclusions. Our data revealed that the EtOAc fraction from D. moldavica L. ethanol extract ameliorates H2O2‐induced cardiotoxicity via antiapoptotic and antioxidant mechanisms.
Cutaneous Lesions in Iranian Neonates and Their Relationships with Maternal-Neonatal Factors: A Prospective Cross-Sectional Study
Authors: Firouzi Hossein , Jalalimehr Iman , Ostadi Zahra , Rahimi Siavash
Published: May 2020

Cutaneous lesions are common in the neonatal period and mostly physiological, transient, and self-limited; uncommonly, they are pathological and require treatment and cooperation between neonatologists and dermatologists. Particular conditions, like prematurity, can influence the onset, type, and evolution of cutaneous manifestations. Of the several articles in the literature about skin findings in newborns, only a few were performed in Iran. We aimed to investigate dermatological findings in a sample of neonates within the first three days of life and to evaluate the association between skin lesions and neonatal- or maternal-related variables. A total of 1202 newborns, hospitalized in the Department of Pediatrics of Imam Sajjad Hospital of Ramsar and Shahid Rajaee Hospital of Tonekabon, Iran, for two years, were examined. All skin findings were recorded, and information on neonatal and maternal variables was collected and analyzed to detect statistically significant associations. Skin lesions were present in 958 newborns (79.8%). The prevalence of milia, erythema toxicum, salmon patch, and Mongolian spots were 45.2%, 43%, 37.3%, and 37%, respectively. Natural vaginal delivery, use of medication, term gestation, and maternal disease were associated with a higher incidence of cutaneous lesions in neonates. Milia, erythema toxicum, Mongolian spots, and genital hyperpigmentation were seen more frequently in the male gender. Conversely, skin desquamation was seen more frequently in females. Among maternal diseases, gestational diabetes mellitus, urinary tract infection, preeclampsia, hypertension, psychiatric disorders, and uterine infection were associated with a higher prevalence of cutaneous lesions. Neonatal cutaneous lesions are a common source of concern in parents and inexperienced physicians. Therefore, prompt recognition of neonatal cutaneous lesions is essential in order to avoid unnecessary diagnostic and therapeutic procedures.
Anti‐Inflammatory and Analgesic Effect of Arachic Acid Ethyl Ester Isolated from Propolis
Authors: Sokeng Sélestin Dongmo , Talla Emmanuel , Sakava Paul , Fokam Tagne Michel Archange , Henoumont Celine , Sophie Laurent , Mbafor Joseph Tanyi , Tchuenguem Fohouo Fernand-Nestor
Published: May 2020

Inflammatory diseases are a real public health problem worldwide. Many synthetic drugs used in the treatment of inflammatory diseases such as steroidal anti‐inflammatory drugs, nonsteroidal anti‐inflammatory drugs (NSAIDs) and immunosuppressive drugs have harmful side effects. However, there are natural products like propolis, which is traditionally used in the treatment of pain. The objective of this work was to evaluate the anti‐inflammatory and analgesic activities of the ethyl ester of arachic acid, a compound isolated from Cameroonian propolis. The ethyl ester of arachic acid was isolated by chromatography of the ethanolic extract of propolis harvested at Tala‐Mokolo (Far North Region of Cameroon) and identified by nuclear magnetic resonance (NMR) spectra and the 1H‐1H correlated spectroscopy. The anti‐inflammatory and analgesic properties of oral administration of arachic acid ethyl ester (12.5, 25.0, and 50.0 mg/kg bw) were evaluated using carrageenan‐induced paw edema, xylene‐induced ear edema, cotton pellets‐induced granuloma formation, and hot plate test in rat. Arachic acid ethyl ester produced maximum inhibition at 50.0 mg/kg for carrageenan‐induced paw edema (62.5%), xylene‐induced ear edema (54.5%), cotton pellet‐induced granuloma (47.4%), and increased mean latency for hot plate test in rats. These results show clearly that the arachic acid ethyl ester has acute and chronic anti‐inflammatory properties as well as central analgesic properties. This justifies the use of propolis in the treatment of pain in traditional medicine.
Two Improved Conjugate Gradient Methods with Application in Compressive Sensing and Motion Control
Authors: Sun Min , Liu Jing , Wang Yaru
Published: May 2020

To solve the monotone equations with convex constraints, a novel multiparameterized conjugate gradient method (MPCGM) is designed and analyzed. This kind of conjugate gradient method is derivative-free and can be viewed as a modified version of the famous Fletcher–Reeves (FR) conjugate gradient method. Under approximate conditions, we show that the proposed method has global convergence property. Furthermore, we generalize the MPCGM to solve unconstrained optimization problem and offer another novel conjugate gradient method (NCGM), which satisfies the sufficient descent property without any line search. Global convergence of the NCGM is also proved. Finally, we report some numerical results to show the efficiency of two novel methods. Specifically, their practical applications in compressive sensing and motion control of robot manipulator are also investigated.
A Novel Algorithm Based on 2-Additive Measure and Shapley Value and Its Application in Land Pollution Remediation
Authors: Lin Jian , Wu Qiongling , Chen Riqing , Tian Zhiyong
Published: May 2020

In this article, a new aggregation operator called the Young–Shapley optimal weight (Y-SOW) operator is proposed to aggregate heterogeneous information in group decision-making. The Y-SOW operator combines the Shapley value with the Young inequality. Meanwhile, a series of special cases and main properties of the Y-SOW operator are studied. Furthermore, the dispersion maximization model of the Y-SOW operator is established to obtain the optimal 2-additive measure. In the Shapley value method of the cooperative game, the 2-additive measure not only simplifies the complexity of fuzzy measures but also solves the interaction between attributes. The Shapley value of the 2-additive measure is explored to the weight of the Y-SOW operator. Finally, the Y-SOW operator-based multiattribute group decision (YSMGAD) algorithm is proposed. The application of the YSMGAD algorithm for land pollution remediation is analyzed.
Decision-Making Support for the Evaluation of Clustering Algorithms Based on MCDM
Authors: Wu Wenshuai , Xu Zeshui , Kou Gang , Shi Yong
Published: May 2020

In many disciplines, the evaluation of algorithms for processing massive data is a challenging research issue. However, different algorithms can produce different or even conflicting evaluation performance, and this phenomenon has not been fully investigated. The motivation of this paper aims to propose a solution scheme for the evaluation of clustering algorithms to reconcile different or even conflicting evaluation performance. The goal of this research is to propose and develop a model, called decision-making support for evaluation of clustering algorithms (DMSECA), to evaluate clustering algorithms by merging expert wisdom in order to reconcile differences in their evaluation performance for information fusion during a complex decision-making process. The proposed model is tested and verified by an experimental study using six clustering algorithms, nine external measures, and four MCDM methods on 20 UCI data sets, including a total of 18,310 instances and 313 attributes. The proposed model can generate a list of algorithm priorities to produce an optimal ranking scheme, which can satisfy the decision preferences of all the participants. The results indicate our developed model is an effective tool for selecting the most appropriate clustering algorithms for given data sets. Furthermore, our proposed model can reconcile different or even conflicting evaluation performance to reach a group agreement in a complex decision-making environment.
Under-Five Mortality in Buea Health District, Southwest Cameroon: Evidence from a Community-Based Birth Cohort Study of Rate, Causes, and Age-Specific Patterns
Authors: Agborndip Ettamba , Kadia Benjamin Momo , Ekaney Domin Sone Majunda , Mbuagbaw Lawrence Tanyi , Obama Marie Therese , Atashili Julius
Published: May 2020

Background. Updating the knowledge base on the causes and patterns of under-five mortality (U5M) is crucial for the design of suitable interventions to improve survival of children under five.Objectives. To assess the rate, causes, and age-specific patterns of U5M in Buea Health District, Cameroon.Methods. A retrospective cohort study involving 2000 randomly selected households was conducted. Live births registered between September 2004 and September 2009 were recorded. The under-five mortality rate (U5MR) was defined by the number of deaths that occurred on or before 5 years of age per 1000 live births. Causes of death were assigned using the InterVA-4 software.Results. A total of 2210 live births were recorded. There were 92 deaths, and the U5MR was 42 per 1000 live births. The mean age at death was11±15.9months. The most frequent causes of death were neonatal causes (37%), malaria (28%), and pneumonia (15%). Deaths during infancy accounted for 64.1% of U5M, with 43.5% neonatal (86% occurring within the first 24 hours of life) and 20.7% postneonatal. The main causes of death in infancy were birth asphyxia (37.5%), pneumonia (17.5%), complications of prematurity (10%), and malaria (10%). Child deaths accounted for 35.8% of U5M. Malaria, pneumonia, and diarrhoeal illnesses accounted for the majority of child deaths.Conclusions. Almost half of U5M occurred during the neonatal period. Improvements in intrapartum care and the prevention and effective treatment of neonatal conditions, malaria, and pneumonia could considerably reduce U5M in Buea.
DNA Vaccine Treatment in Dogs Experimentally Infected with Trypanosoma cruzi
Authors: Arce-Fonseca Minerva , Carbajal-Hernández Ana C. , Lozano-Camacho Mónica , Carrillo-Sánchez Silvia del C. , Roldán Francisco-Javier , Aranda-Fraustro Alberto , Rosales-Encina José Luis , Rodríguez-Morales Olivia
Published: May 2020

Chagas disease is a chronic and potentially lethal disorder caused by the parasite Trypanosoma cruzi, and an effective treatment has not been developed for chronic Chagas disease. The objective of this study was to determine the effectiveness of a therapeutic DNA vaccine containing T. cruzi genes in dogs with experimentally induced Chagas disease through clinical, pathological, and immunological analyses. Infection of Beagle dogs with the H8 T. cruzi strain was performed intraperitoneally with 3500 metacyclic trypomastigotes/kg body weight. Two weeks after infection, plasmid DNA immunotherapy was administered thrice at 15-day intervals. The clinical (physical and cabinet studies), immunological (antibody and cytokine profiles and lymphoproliferation), and macro- and microscopic pathological findings were described. A significant increase in IgG and cell proliferation was recorded after immunotherapy, and the highest stimulation index (3.02) was observed in dogs treated with the pBCSSP4 plasmid. The second treatment with both plasmids induced an increase in IL-1, and the third treatment with the pBCSSP4 plasmid induced an increase in IL-6. The pBCSP plasmid had a good Th1 response regulated by high levels of IFN-gamma and TNF-alpha, whereas the combination of the two plasmids did not have a synergistic effect. Electrocardiographic studies registered lower abnormalities and the lowest number of individuals with abnormalities in each group treated with the therapeutic vaccine. Echocardiograms showed that the pBCSSP4 plasmid immunotherapy preserved cardiac structure and function to a greater extent and prevented cardiomegaly. The two plasmids alone controlled the infection moderately by a reduction in the inflammatory infiltrates in heart tissue. The immunotherapy was able to reduce the magnitude of cardiac lesions and modulate the cellular immune response; the pBCSP treatment showed a clear Th1 response; and pBCSSP4 induced a balanced Th1/Th2 immune response that prevented severe cardiac involvement. The pBCSSP4 plasmid had a better effect on most of the parameters evaluated in this study; therefore, this plasmid can be considered an optional treatment against Chagas disease in naturally infected dogs.
Changes in Colorectal Cancer 5-Year Survival Disparities in California, 1997–2014
Authors: Oh Debora L. , Santiago-Rodríguez Eduardo J. , Canchola Alison J. , Ellis Libby , Tao Li , Gomez Scarlett L.
Published: May 2020

Background:

Colorectal cancer incidence and mortality have declined with increased screening and scientific advances in treatment. However, improvement in colorectal cancer outcomes has not been equal for all groups and disparities have persisted over time.

Methods:

Data from the California Cancer Registry were used to estimate changes in 5-year colorectal cancer–specific survival over three diagnostic time periods: 1997–2002, 2003–2008, and 2009–2014. Analyses included all patients in California with colorectal cancer as a first primary malignancy. Multivariable Cox proportional hazard regression models were used to evaluate the effect of race/ethnicity, insurance status, and neighborhood socioeconomic status (nSES) on 5-year colorectal cancer–specific survival.

Results:

On the basis of a population-based sample of 197,060 colorectal cancer cases, racial/ethnic survival disparities decreased over time among non-Hispanic Blacks (NHB) compared with non-Hispanic Whites (NHW), after adjusting for demographic, clinical, and treatment characteristics. For cases diagnosed 1997–2002, colorectal cancer–specific hazard rates were higher for NHB [HR, 1.12; 95% confidence interval (CI), 1.06–1.19] and lower for Asians/Pacific Islanders (HR, 0.92; 95% CI, 0.87–0.96) and Hispanics (HR, 0.94; 95% CI, 0.90–0.99) compared with NHW. In 2009–2014, colorectal cancer–specific HR for NHB was not significantly different to the rate observed for NHW (HR, 1.03; 95% CI, 0.97–1.10). There were no changes in disparities in nSES, but increasing disparities by health insurance status.

Conclusions:

We found a decrease in survival disparities over time by race/ethnicity, but a persistence of disparities by neighborhood socioeconomic status and health insurance status.

Impact:

Further investigation into the drivers for these disparities can help direct policy and practice toward health equity for all groups.
The COronavirus Pandemic Epidemiology (COPE) Consortium: A Call to Action
Authors: Chan Andrew T. , Drew David A. , Nguyen Long H. , Joshi Amit D. , Ma Wenjie , Guo Chuan-Guo , Lo Chun-Han , Mehta Raaj S. , Kwon Sohee , Sikavi Daniel R. , Magicheva-Gupta Marina V. , Fatehi Zahra S. , Flynn Jacqueline J. , Leonardo Brianna M. , Albert Christine M. , Andreotti Gabriella , Beane-Freeman Laura E. , Balasubramanian Bijal A. , Brownstein John S. , Bruinsma Fiona , Cowan Annie N. , Deka Anusila , Ernst Michael E. , Figueiredo Jane C. , Franks Paul W. , Gardner Christopher D. , Ghobrial Irene M. , Haiman Christopher A. , Hall Janet E. , Deming-Halverson Sandra L. , Kirpach Brenda , Lacey James V. , Marchand Loïc Le , Marinac Catherine R. , Martinez Maria Elena , Milne Roger L. , Murray Anne M. , Nash Denis , Palmer Julie R. , Patel Alpa V. , Rosenberg Lynn , Sandler Dale P. , Sharma Shreela V. , Schurman Shepherd H. , Wilkens Lynne R. , Chavarro Jorge E. , Eliassen A. Heather , Hart Jaime E. , Kang Jae Hee , Koenen Karestan C. , Kubzansky Laura D. , Mucci Lorelei A. , Ourselin Sebastien , Rich-Edwards Janet W. , Song Mingyang , Stampfer Meir J. , Steves Claire J. , Willett Walter C. , Wolf Jonathan , Spector Tim
Published: May 2020

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.
Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I Trials
Authors: Shi Donghua , Shi Yaoping , Kaseb Ahmed O. , Qi Xingxing , Zhang Yuan , Chi Jiachang , Lu Qing , Gao Huiping , Jiang Hua , Wang Huamao , Yuan Daijing , Ma Hong , Wang Hongyang , Li Zonghai , Zhai Bo
Published: May 2020

Purpose:

Our preclinical studies demonstrated the potential of chimeric antigen receptor (CAR)-glypican-3 (GPC3) T-cell therapy for hepatocellular carcinoma (HCC). We report herein the first published results of CAR-GPC3 T-cell therapy for HCC.

Patients and Methods:

In two prospective phase I studies, adult patients with advanced GPC3+ HCC (Child-Pugh A) received autologous CAR-GPC3 T-cell therapy following cyclophosphamide- and fludarabine-induced lymphodepletion. The primary objective was to assess the treatment's safety. Adverse events were graded using the Common Terminology Criteria for Adverse Events (version 4.03). Tumor responses were evaluated using the RECIST (version 1.1).

Results:

A total of 13 patients received a median of 19.9 × 108 CAR-GPC3 T cells by a data cutoff date of July 24, 2019. We observed pyrexia, decreased lymphocyte count, and cytokine release syndrome (CRS) in 13, 12, and nine patients, respectively. CRS (grade 1/2) was reversible in eight patients. One patient experienced grade 5 CRS. No patients had grade 3/4 neurotoxicity. The overall survival rates at 3 years, 1 year, and 6 months were 10.5%, 42.0%, and 50.3%, respectively, according to the Kaplan–Meier method. We confirmed two partial responses. One patient with sustained stable disease was alive after 44.2 months. CAR T-cell expansion tended to be positively associated with tumor response.

Conclusions:

This report demonstrated the initial safety profile of CAR-GPC3 T-cell therapy. We observed early signs of antitumor activity of CAR-GPC3 T cells in patients with advanced HCC.
NSABP B-41, a Randomized Neoadjuvant Trial: Genes and Signatures Associated with Pathologic Complete Response
Authors: Swain Sandra M. , Tang Gong , Brauer Heather Ann , Goerlitz David S. , Lucas Peter C. , Robidoux André , Harris Brent T. , Bandos Hanna , Ren Yuqi , Geyer Charles E. , Rastogi Priya , Mamounas Eleftherios P. , Wolmark Norman
Published: May 2020

Purpose:

In NSABP B-41, pathologic complete response (pCR) was associated with prolonged survival among women with HER2-positive operable breast cancer treated with neoadjuvant chemotherapy and lapatinib, trastuzumab, or the combination. We used a large human breast cancer gene expression panel to select candidate prognostic biomarkers for pCR among women treated with trastuzumab in NSABP B-41.

Patients and Methods:

Eligible patients had a baseline preadjuvant treatment core biopsy sample, known pCR status, and no withdrawal of consent. We analyzed extracted RNA using the human nCounter Breast Cancer 360 gene expression panel. Gene counts were normalized to housekeeping genes and transformed into logarithmic scale with base 2. To screen for candidate genes and metagene signatures prognostic of pCR, we used univariate logistic regression. Variable selection was done by multivariable logistic regression with lasso regularization.

Results:

Analyses of data from 130 patients revealed that a composite of gene expression from 19 genes and one gene signature appeared to predict pCR in women with HER2-positive early-stage breast cancer undergoing neoadjuvant chemotherapy with trastuzumab-containing regimens. The identified genes are involved in important pathways such as epithelial–mesenchymal transition, adhesion and migration, estrogen receptor signaling, DNA damage and repair, apoptosis, and proliferation. The AUC from a 10-fold cross-validation on predicting pCR, with these 20 genomic markers in a logistic regression model, was 0.73.

Conclusions:

The expression level of ERBB2, ESR1, and a few other genomic markers was highly predictive of pCR after trastuzumab-containing regimens. These findings need to be validated and calibrated in future studies.
Concurrent Definitive Immunoradiotherapy for Patients with Stage III–IV Head and Neck Cancer and Cisplatin Contraindication
Authors: Weiss Jared , Sheth Siddharth , Deal Allison M. , Grilley Olson Juneko E. , Patel Samip , Hackman Trevor G. , Blumberg Jeffrey M. , Galloway Thomas J. , Patel Shetal , Zanation Adam M. , Shen Colette J. , Hayes D. Neil , Hilliard Christopher , Mehra Ranee , McKinnon Karen P. , Wang Hsing-Hui , Weissler Mark Christian , Bauman Jessica R. , Chera Bhishamjit S. , Vincent Benjamin G.
Published: May 2020

Purpose:

Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti–PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC.

Patients and Methods:

This single-arm, multi-institution, phase II study (NCT02609503) enrolled 29 cisplatin-ineligible patients. Patients received radiotherapy concurrently with three cycles of pembrolizumab 200 mg every 3 weeks followed by three adjuvant cycles. The primary endpoint was a progression-free survival (PFS) of ≥16 months. Correlative studies included peripheral blood flow cytometry and Luminex cytokine profiling.

Results:

Reasons for cisplatin ineligibility included otopathy (69.0%), nephropathy (20.7%), and neuropathy (6.9%). With median follow-up of 21 months, estimated 24-month PFS and overall survival rates were 71% (95% confidence interval, 49%–84%) and 75% (51%–88%). The primary PFS endpoint has exceeded the hypothesis and its median has not been reached. Toxicities were typical of radiotherapy; however, high rates of grade 3/4 lymphopenia (58.6%) were observed. Flow cytometry revealed a relative decline in CD4 T cells and B cells, but not CD8 T cells. Upon treatment, frequencies of transitional B cells and tissue-like memory B cells increased, while resting memory B cells decreased. Patients with progression had greater percentages of baseline naïve B cells and fewer marginal zone B cells.

Conclusions:

Pembrolizumab and radiotherapy is efficacious in LA-HNSCC and should be evaluated in a randomized trial. The observed changes in B-cell markers deserve further study both as potential biomarkers and as therapeutic targets.
Functional miRNA Screening Identifies Wide-ranging Antitumor Properties of miR-3622b-5p and Reveals a New Therapeutic Combination Strategy in Ovarian Tumor Organoids
Authors: Vernon Mégane , Lambert Bernard , Meryet-Figuière Matthieu , Brotin Emilie , Weiswald Louis-Bastien , Paysant Hippolyte , Vigneron Nicolas , Wambecke Anaïs , Abeilard Edwige , Giffard Florence , Louis Marie-Hélène , Blanc-Fournier Cécile , Gauduchon Pascal , Poulain Laurent , Denoyelle Christophe
Published: May 2020

Novel therapeutic strategies are urgently required for the clinical management of chemoresistant ovarian carcinoma, which is the most lethal of the gynecologic malignancies. miRNAs hold promise because they play a critical role in determining the cell phenotype by regulating several hundreds of targets, which could constitute vulnerabilities of cancer cells. A combination of gain-of-function miRNA screening and real-time continuous cell monitoring allows the identification of miRNAs with robust cytotoxic effects in chemoresistant ovarian cancer cells. Focusing on miR-3622b-5p, we show that it induces apoptosis in several ovarian cancer cell lines by both directly targeting Bcl-xL and EGFR-mediating BIM upregulation. miR-3622b-5p also sensitizes cells to cisplatin by inhibiting Bcl-xL in ovarian cancer cell lines escaping BIM induction. miR-3622b-5p also exerts antimigratory capacities by targeting both LIMK1 and NOTCH1. These wide-ranging antitumor properties of miR-3622b-5p in ovarian cancer cells are mimicked by the associations of pharmacologic inhibitors targeting these proteins. The combination of an EGFR inhibitor together with a BH3-mimetic molecule induced a large decrease in cell viability in a panel of ovarian cancer cell lines and several ovarian patient-derived tumor organoids, suggesting the value of pursuing such a combination therapy in ovarian carcinoma. Altogether, our work highlights the potential of phenotype-based miRNA screening approaches to identify lethal interactions which might lead to new drug combinations and clinically applicable strategies.