bluuebunny/crossref_metadata_2025 huggingface dataset:
Detecting Intergranular Phases in UNS N07725. Part II: Double-Loop Electrochemical Potentiokinetic Reactivation Test Validation
Authors: Hazarabedian Maria Sofia , Quadir Md Zakaria , Iannuzzi Mariano
Published: March 2021

The formation of interconnected grain boundary (GB) phases in precipitation hardening (PH) nickel Alloy 725 (UNS N07725) compromises its mechanical properties and has been linked to hydrogen embrittlement failures. However, normative industry standards such as API 6ACRA are inadequate for differentiating between Alloy 725 batches with a critical extent of GB precipitation, creating the need for a complementary qualification method.

In Alloy 725, intergranular phases produce a Cr and Mo depletion adjacent to GBs (i.e., sensitization). In Part I of this work, this impoverishment in Cr and Mo was used as the basis to develop a double-loop electrochemical potentiokinetic reactivation (DL-EPR) test, optimized to quantify the extent of GB precipitation in Alloy 725. Part II explores the reproducibility and sensitivity of the new approach using three new independent commercial batches containing different extents of precipitation. Results were highly reproducible and confirmed the method’s sensitivity to detect small amounts of GB phases. Additionally, the DL-EPR procedure revealed clear microstructural inhomogeneities across the bars’ thickness, which increased with increasing bar diameter. This investigation strongly supports the validity of the new DL-EPR technique as a reliable and straightforward industry-friendly qualification method to quantify the extent of intergranular phases in Alloy 725.
Soluble guanylate cyclase stimulation in late gestation does not mitigate asymmetric intrauterine growth restriction or cardiovascular risk induced by placental ischemia in the rat
Authors: Coats Laura E. , Bakrania Bhavisha A. , Bamrick-Fernandez Daniel R. , Ariatti Allison M. , Rawls Adam Z. , Ojeda Norma B. , Alexander Barbara T.
Published: March 2021

The importance of the soluble guanylate cyclase-cGMP pathway in a rat model of placental ischemia differs during critical windows of development, implicating other factors may be critical mediators of impaired fetal growth in the final stages of gestation. Moreover, increased blood pressure at 4 mo of age in male intrauterine growth restriction offspring is associated with impaired cardiac function including an increase in global longitudinal strain in conjunction with a decrease in stroke volume, ejection fraction, and cardiac output.
[Retracted] Upregulating hsa‐miR‐128a Increased the Effects of Pembrolizumab on Laryngeal Cancer Cells via the p53 Pathway
Authors: Chen Hui , Guo Yang , Huang Jiameng , Zhou Liang
Published: March 2021

Objectives. Recently, immunotherapy and microRNA have shown much more promises in oncology research, inspiring new hope for a cure for various malignancies. Specifically, the function and mechanisms of action of pembrolizumab have been investigated in many cancers, but not in laryngeal squamous cell carcinoma. The present study thus focused on the effect of hsa‐miR‐128a on pembrolizumab in laryngeal cancer cells as well as tried to elucidate the mechanisms that may mediate this effect. Methods. Hep2 and AMC‐HN8 cell lines were utilized to create stable cell lines that overexpressing hsa‐miR‐128a. Using the immunotherapy assay, the contribution of hsa‐miR‐128a to pembrolizumab sensitivity was evaluated. By performing the dual luciferase assay and quantitative real‐time polymerase chain reaction, the possible mechanisms of hsa‐miR‐128a were identified. Results. Hsa‐miR‐128a was overexpressed in laryngeal cancer cell lines successfully. The immunotherapy assay revealed that upregulating hsa‐miR‐128a augmented the effect of pembrolizumab. Moreover, hsa‐miR‐128a targeted BMI‐1 and might played a role in the p53 pathway. Conclusion. Hsa‐miR‐128a boosted the effect of pembrolizumab on laryngeal cancer cells, perhaps via the p53 pathway. Therefore, hsa‐miR‐128a might be a novel target in laryngeal cancer treatment.
Study on the Parameter Equation of Coal and Gas Outburst Hole
Authors: Wang Fei , Yang Yuzhong , Wu Liyun , Meng Han , Peng Lei
Published: March 2021

Studying the parameters of a coal and gas hole (CGOH), such as the hole shape, hole size and volume, coal quantity of CGOH, coal throw distance, calculated hole density, and gas pressure, is helpful in revealing the coal and gas outburst mechanism. In this study, we found that there were close mathematical relationships between these parameters. A nonlinear composite function relationship (CGOH parameter equation) was observed between the coal quantity, CGOH volume, and throw distance. The correctness of these relationships was verified using the Origin software. The stagnation point and inflection point of the parameter curve were obtained through the derivation of the parameter equation, and the transformation path from coal and gas outburst to coal and gas extrusion or dumping was clarified. At the same time, the equations of gas pressure, coal quantity, and throw distance are derived.
Deep Learning Algorithm‐Based Financial Prediction Models
Authors: Jia Helin
Published: March 2021

In this paper, a new FEPA portfolio forecasting model is based on the EMD decomposition method. The model is based on the special empirical modal decomposition of financial time series, principal component analysis, and artificial neural network to model and forecast for nonlinear, nonstationary, multiscale complex financial time series to predict stock market indices and foreign exchange rates and empirically investigate this hot area in financial market research. The combined forecasting model proposed in this paper is based on the idea of decomposition‐reconstruction synthesis, which effectively improves the model’s prediction of internal financial time series. In this paper, we select the CSI 300 Index and foreign exchange rate as the empirical market and data and establish seven forecasting models to make predictions about the short‐term running trend of the closing price. The interval EMD decomposition algorithm is introduced in this paper, considering both high and low prices to be contained in the input and output. By analyzing the closing price, high and low prices of the stock index at the same time, the volatility of this interval time series of the index and its trend can be better captured.
Complex Dynamics and Hard Limiter Control of a Fractional-Order Buck-Boost System
Authors: Yan Bo , Wang Shaojie , He Shaobo
Published: March 2021

Chaos and control analysis for the fractional-order nonlinear circuits is a recent hot topic. In this study, a fractional-order model is deduced from a Buck-Boost converter, and its discrete solution is obtained based on the Adomian decomposition method (ADM). Chaotic dynamic characteristics of the fractional-order system are investigated by the bifurcation diagram, 0-1 test, spectral entropy (SE) algorithm, and NIST test. Meanwhile, the control of the fractional-order Buck-Boost model is discussed through two different ways, namely, the intensity feedback and the hard limiter control. Specifically, the hard limiter control can be realized using a current limiter in the circuit, where the current limiter device is applied to control the branch current. The results show that the proposed fractional-order system has complex dynamic behaviors and potential application values in the engineering field.
The Location of the Fibular Tunnel for Anatomically Accurate Reconstruction of the Lateral Ankle Ligament: A Cadaveric Study
Authors: Park Jeong-Hyun , Kwon Hyung-Wook , Kim Digud , Park Kwang-Rak , Lee Mijeong , Choi Yu-Jin , Cho Jaeho
Published: March 2021

We aimed to describe the location of fibular footprint of each anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL), as well as their common origin in relation to bony landmarks of the fibula in order to determine the location of the fibular tunnel. In 105 ankle specimens, the center of the footprints of the ATFL and CFL (cATFL and cCFL, respectively) and the intersection point of their origin (intATFL‐CFL) were investigated, and the distances from selected bony landmarks (the articular tip (AT) and the inferior tip (IT) of the fibula) were measured. Forty‐two (40%) specimens had single‐bundle ATFL, and 63 (60%) had double‐bundle patterns. The distance between intATFL‐CFL and IT was 12.0 ± 2.5 mm, and a significant difference was observed between the two groups (p = 0.001). Moreover, the ratio of the intATFL‐CFL location based on the anterior fibular border for all cadavers was 0.386. The present study suggests a reference ratio that can help surgeons locate the fibular tunnel for a more anatomically accurate reconstruction of the lateral ankle ligament. Also, it may be necessary to make a difference in the location of the fibular tunnel according to the number of ATFL bundles during surgery.
Three-Dimensional Rotating Flow of MHD Jeffrey Fluid Flow between Two Parallel Plates with Impact of Hall Current
Authors: Fiza Mehreen , Alsubie Abdelaziz , Ullah Hakeem , Hamadneh Nawaf N. , Islam Saeed , Khan Ilyas
Published: March 2021

This article deals with three-dimensional non-Newtonian Jeffrey fluid in rotating frame in the presence of magnetic field. The flow is studied in the application of Hall current, where the flow is assumed in steady states. The upper plate is considered fixed, and the lower is kept stretched. The fundamental equations are transformed into a set of ordinary differential equations (ODEs). A homotopy technique is practiced for a solution. The variation in the skin friction and its effects on the velocity fields have been examined numerically. The effects of physical parameters are discussed in various plots.
Determination of Cutoff Values for the Screening of Osteosarcopenia in Obese Postmenopausal Women
Authors: Abidin Nurdiana Z. , Mitra Soma R.
Published: March 2021

Osteosarcopenic obesity (OSO) describes the concurrent presence of obesity, low bone mass, and low muscle mass in an individual. Currently, no established criteria exist to diagnose OSO. We hypothesized that obese individuals require different cut-points from standard cut-points to define low bone mass and low muscle mass due to their higher weight load. In this study, we determined cutoff values for the screening of osteosarcopenia (OS) in obese postmenopausal Malaysian women based on the measurements of quantitative ultrasound (QUS), bioelectrical impedance analysis (BIA), and functional performance test. Then, we compared the cutoff values derived by 3 different statistical modeling methods, (1) receiver operating characteristic (ROC) curve, (2) lowest quintile of the study population, and (3) 2 standard deviations (SD) below the mean value of a young reference group, and discussed the most suitable method to screen for the presence of OS in obese population. One hundred and forty-one (n = 141) postmenopausal Malaysian women participated in the study. Bone density was assessed using calcaneal quantitative ultrasound. Body composition was assessed using bioelectrical impedance analyzer. Handgrip strength was assessed using a handgrip dynamometer, and physical performance was assessed using a modified Short Physical Performance Battery test. ROC curve was determined to be the most suitable statistical modeling method to derive the cutoffs for the presence of OS in obese population. From the ROC curve method, the final model to estimate the probability of OS in obese postmenopausal women is comprised of five variables: handgrip strength (HGS, with area under the curve (AUC) = 0.698 and threshold ≤ 16.5 kg), skeletal muscle mass index (SMMI, AUC = 0.966 and threshold ≤ 8.2 kg/m2), fat-free mass index (FFMI, AUC = 0.946 and threshold ≤ 15.2 kg/m2), broadband ultrasonic attenuation (BUA, AUC = 0.987 and threshold ≤ 52.85 dB/MHz), and speed of sound (SOS, AUC = 0.991 and threshold ≤ 1492.15 m/s). Portable equipment may be used to screen for OS in obese women. Early identification of OS can help lower the risk of advanced functional impairment that can lead to physical disability in obese postmenopausal women.
Safety and Efficacy of Transcatheter Occlusion of Perimembranous Ventricular Septal Defect with Aortic Valve Prolapse: A Six-Year Follow-Up Study
Authors: Zhang Wenqian , Wang Chaojie , Liu Shenrong , Zhou Lingmei , Li Junjie , Shi Jijun , Qian Mingyang , Wang Shushui , Xie Yu-Mei , Zhang Zhiwei
Published: March 2021

Background. With the rapid development of transcatheter techniques and instruments, transcatheter occlusion for patients with perimembranous ventricular septal defect (pVSD) and aortic valve prolapse (AVP) was constantly being tried, while the efficacy and safety of pVSD with AVP remain controversial. Objective. The aim of this study was to evaluate long-term efficacy and safety of transcatheter occlusion of pVSD with AVP. Methods. We retrospectively analyzed 164 children with pVSD and AVP who underwent transcatheter occlusion between January 2013 and November 2014. AVP was divided into 3 degrees according to right coronary leaflet morphology at end-diastole during aortic root angiography. Patient demographic and clinical data were collected. Results. There were 97 males and 67 females (median age, 40.0 (30.0–62.7) months; average weight, 16.94 ± 9.02 kg). Mild (n = 63), moderate (n = 89), and severe (n = 12) AVP success rates were 93.7%, 89.9%, and 58.3%, respectively. Immediately after procedure, there was no new-onset aortic regurgitation (AR) above trivial degree, residual shunt above mild degree, or complications requiring medication or operation, except for 1 patient who developed transient complete atrioventricular block. During follow-up, 1 mild AVP patient aggravated from mild to moderate AR and 1 moderate AVP patient aggravated from trivial to moderate AR. The new-onset AR in mild, moderate, and severe AVP was 2%, 1.8%, and 20%, respectively. AR disappeared in 17 patients. Residual shunt occurred in 9 patients after procedure, 4 of which disappeared during the follow-up period. No serious complications occurred in any patient during follow-up. Five-year cardiovascular event-free survival rates for mild, moderate, and severe AVP were 89.6%, 94.5%, and 80.0%, respectively. Conclusion. Transcatheter occlusion of pVSD with mild and moderate AVP has a high success rate and few complications, which is safe and effective in long-term follow-up. Transcatheter occlusion of pVSD with severe AVP has low success rates and high AR incidence. Therefore, transcatheter occlusion of pVSD with AVP is recommended for mild to moderate, but not severe, AVP.
Inelastic Form Factor Calculations for 46,48,50Ti Isotopes Using Tassie Model
Authors: Oleiwi Mohanad H.
Published: March 2021

Inelastic form factors of electrical transition have been calculated for 46,48,50Ti isotopes using the Tassie model. The form factors have been calculated for different exciting energies. The harmonic oscillator (HO) wave function has been used as a single-particle wave function. The model space has been considered as 1f7/2, 2p3/2, 2p1/2, and 2f5/2. Gx1 has been used as effective interaction in all calculations. In all calculations, the effective charge has been considered as 1.5e for proton and 0.5e for neutron. All obtained results have been compared with data from an experiment. The calculations show the Tassie model gives a good description of longitudinal form factors of 46,48,50Ti isotopes in E(2+) transitions as compared with experimental data, especially in the region below 2 fm−1 of momentum transfer, but in the E(4+), the theoretical results deviated slightly from experimental data especially in the region greater than 1.5 fm−1 of momentum transfer.
Vehicle Reidentification via Multifeature Hypergraph Fusion
Authors: Li Wang , Yong Zhang , Wei Yuan , Hongxing Shi
Published: March 2021

Vehicle reidentification refers to the mission of matching vehicles across nonoverlapping cameras, which is one of the critical problems of the intelligent transportation system. Due to the resemblance of the appearance of the vehicles on road, traditional methods could not perform well on vehicles with high similarity. In this paper, we utilize hypergraph representation to integrate image features and tackle the issue of vehicles re-ID via hypergraph learning algorithms. A feature descriptor can only extract features from a single aspect. To merge multiple feature descriptors, an efficient and appropriate representation is particularly necessary, and a hypergraph is naturally suitable for modeling high-order relationships. In addition, the spatiotemporal correlation of traffic status between cameras is the constraint beyond the image, which can greatly improve the re-ID accuracy of different vehicles with similar appearances. The method proposed in this paper uses hypergraph optimization to learn about the similarity between the query image and images in the library. By using the pair and higher-order relationship between query objects and image library, the similarity measurement method is improved compared to direct matching. The experiments conducted on the image library constructed in this paper demonstrates the effectiveness of using multifeature hypergraph fusion and the spatiotemporal correlation model to address issues in vehicle reidentification.
Cuckoo Search-based SVM (CS-SVM) Model for Real-Time Indoor Position Estimation in IoT Networks
Authors: Khan Amjad , Khan Asfandyar , Bangash Javed Iqbal , Subhan Fazli , Khan Abdullah , Khan Atif , Uddin M. Irfan , Mahmoud Marwan
Published: March 2021

Internet of Things (IoT), an emerging technology, is becoming an essential part of today’s world. Machine learning (ML) algorithms play an important role in various applications of IoT. For decades, the location information has been extremely useful for humans to navigate both in outdoor and indoor environments. Wi-Fi access point-based indoor positioning systems get more popularity, as it avoids extra calibration expenses. The fingerprinting technique is preferred in an indoor environment as it does not require a signal’s Line of Sight (LoS). It consists of two phases: offline and online phase. In the offline phase, the Wi-Fi RSSI radio map of the site is stored in a database, and in the online phase, the object is localized using the offline database. To avoid the radio map construction which is expensive in terms of labor, time, and cost, machine learning techniques may be used. In this research work, we proposed a hybrid technique using Cuckoo Search-based Support Vector Machine (CS-SVM) for real-time position estimation. Cuckoo search is a nature-inspired optimization algorithm, which solves the problem of slow convergence rate and local minima of other similar algorithms. Wi-Fi RSSI fingerprint dataset of UCI repository having seven classes is used for simulation purposes. The dataset is preprocessed by min-max normalization to increase accuracy and reduce computational speed. The proposed model is simulated using MATLAB and evaluated in terms of accuracy, precision, and recall with K-nearest neighbor (KNN) and support vector machine (SVM). Moreover, the simulation results show that the proposed model achieves high accuracy of 99.87%.
Feasibility Study of the “HemoTypeSC” Test for the Rapid Screening of Sickle Cell Disease in Côte D’Ivoire
Authors: Kakou Danho Jeannette Bassimbié , Atiméré Yao Nicaise , Koné Daouda , Yéo Donafologo Daouda , Couitchéré Line
Published: March 2021

Sickle cell disease is a hereditary disease that predominantly affects black people. It is very widespread in sub-Saharan Africa, particularly at the Lehmann “sickle belt” level, where the prevalence of the hemoglobin S involves at least 10% of the population in West Africa and can reach 40% in Central Africa. In Côte d’Ivoire, the prevalence of the hemoglobin S is about 12–14% in the general population and about 11.71% in the child population in Abidjan. On the other hand, its coexistence with other hemoglobin phenotypes such as AC (6.2%) and β-thalassemia (2.7%) traits may also cause composite heterogeneous sickle cell disease, e.g., SC or S/β-thalassemia in this study. Since 2009, sickle cell disease has been recognized as a public health problem; however, much still remains to be performed despite the progress achieved. The objective of this study is thus to promote a rapid screening for the struggling against sickle cell disease in Côte d’Ivoire. This study was carried out over 6 months (April–September 2019) and has included 336 children, of which 236 all-comers, recruited in the municipality of Treichville in Abidjan and 100 other children with already known hemoglobin phenotype followed up in the Hematology Department of the University Hospital of Treichville. Two tests were used: the HemoTypeSC™ for rapid screening and the hemoglobin electrophoresis which is the reference method used for confirming the diagnosis in the laboratory. The findings confirmed the reliability of the HemoTypeSC™ with a sensitivity and specificity at 100% for the detection of hemoglobin A, S, and C. On the other hand, this sensitivity and specificity drop to 98.2% and 99.7%, respectively, when we analyze all the 336 children together, including the cases with HbF detected by hemoglobin electrophoresis. Hence, the importance of performing certainty tests following the HemoTypeSC™ screening test in order to determine the accurate phenotypes and proportions of the types of hemoglobin. The prevalence of hemoglobin S in subgroup 1 of 236 children of all-comers was 15%. The HemoTypeSC™ is therefore reliable, inexpensive, and disposable for rapid screening and early detection of sickle cell disease in Côte d’Ivoire. The HemoTypeSC™ provides rapid detection of hemoglobin phenotypes HbAA, HbSS, HbSC, HbCC, HbAS, and HbAC.
Effect of Vitamin D Status on Vascular Function of the Aorta in a Rat Model of PCOS
Authors: Lajtai K. , Tarszabó R. , Bányai B. , Péterffy B. , Gerszi D. , Ruisanchez É. , Sziva R. E. , Korsós-Novák Á. , Benkő R. , Hadjadj L. , Benyó Z. , Horváth E. M. , Masszi G. , Várbíró S.
Published: March 2021

Polycystic ovary syndrome (PCOS) is associated with elevated cardiovascular risk. Early vascular dysfunction may lead to the development of cardiovascular disease in PCOS. Vitamin D deficiency (VDD) is a common comorbidity of PCOS that contributes to the pathogenesis of the disease and its complications. Both PCOS and VDD are accompanied by increased oxidative stress that may be involved in the arising vascular dysfunction. We aimed to investigate the role of vitamin D status on aortic function. PCOS was induced by an 8‐week‐long transdermal testosterone treatment of female rats, and low and adequate vitamin D status was achieved by dietary means. Contraction and relaxation abilities of isolated aortic segments were measured by myograph. Resorcin‐fuchsin staining and immunohistochemical labeling of 3‐nitrotyrosine were performed. No difference was shown in the norepinephrine‐induced contraction of the aortas of different groups, whereas we detected reduced acetylcholine‐ and insulin‐evoked relaxation in VDD groups. A lower level of resorcin‐fuchsin staining and elevated 3‐nitrotyrosine immunostaining was observed in VDD. In our study, we demonstrated early endothelial dysfunction in VDD PCOS rat model. Vitamin D supplementation could prevent vascular disturbances, while VDD itself damaged endothelium‐dependent vasorelaxation and induced nitrative stress.
Hierarchical Annotation Event Extraction Method in Multiple Scenarios
Authors: Wang Shi , Wang Zhujun , Jiang Yi , Wang Huayu
Published: March 2021

In the event extraction task, considering that there may be multiple scenarios in the corpus and an argument may play different roles under different triggers, the traditional tagging scheme can only tag each word once, which cannot solve the problem of argument overlap. A hierarchical tagging pipeline model for Chinese corpus based on the pretrained model Bert was proposed, which can obtain the relevant arguments of each event in a hierarchical way. The pipeline structure is selected in the model, and the event extraction task is divided into event trigger classification and argument recognition. Firstly, the pretrained model Bert is used to generate the feature vector and transfer it to bidirectional gated recurrent unit+conditional random field (BiGRU+CRF) model for trigger classification; then, the marked event type features are spliced into the corpus as known features and then passed into BiGRU+CRF for argument recognition. We evaluated our method on DUEE, combined with data enhancement and mask operation. Experimental results show that our method is improved compared with other baselines, which prove the effectiveness of the model in Chinese corpus.
Observations on the Efficacy of Two Methods for the Treatment of Upper Eyelid Retraction in Thyroid‐Associated Ophthalmopathy
Authors: Li Dongping , Sun Fengyuan
Published: March 2021

Objective. To observe the clinical efficacy of periocular injection of triamcinolone acetonide (TA) and subpalpebral injection of botulinum toxin type A (BTXA) for the treatment of thyroid‐associated ophthalmopathy (TAO) with mild unilateral upper eyelid retraction. Method. This was a prospective randomized controlled study. A total of 68 cases of stable thyroid‐associated ophthalmopathy with mild upper eyelid retraction were collected at Hankou Aier Eye Hospital from Jan. 2015 to Dec. 2018 and randomly divided into two groups. Group A contained 33 patients who were administered TA by periocular injection once every 3 weeks for a total of 3 times. Group B contained 35 patients who were given a single subpalpebral administration of BTXA. The efficacy in the two groups was observed. Results. Compared with the two groups, the effective rate in both groups was 100% at 1 week and 1 month after treatment. The effective rate of Group A remained 100% at 3 months after treatment, and that of Group B decreased to 88.6%. At 1 week after treatment, the degree of correction in Group B was greater than that in Group A (p < 0.001). At 1 month after treatment, it was not significantly different between the two groups (p > >>0.05). At 3 months after treatment, it was less in Group B than in Group A (p < 0.001). In Group A, there was one case of transient amaurosis, two cases of periorbital hemorrhage and swelling, and one mild case of sunken eyes. In Group B, four cases experienced recurrence after 3 months. Conclusion. Periocular injection of TA and subpalpebral injection of BTXA offer definite therapeutic efficacy for mild upper eyelid retraction associated with thyroid disease. The former has a long treatment period, large procedural risks, and stable efficacy. The latter is a simple procedure with a short treatment period but can easily recur.
A Phase Ib Open-Label, Dose-Escalation Study of NUC-1031 in Combination with Carboplatin for Recurrent Ovarian Cancer
Authors: Kazmi Farasat , Nicum Shibani , Roux Rene L. , Spiers Laura , Gnanaranjan Chat , Sukumaran Ajithkumar , Gabra Hani , Ghazaly Essam , McCracken Nigel W. , Harrison David J. , Blagden Sarah P.
Published: March 2021

Purpose:

NUC-1031 is a first-in-class ProTide modification of gemcitabine. In PRO-002, NUC-1031 was combined with carboplatin in recurrent ovarian cancer.

Patients and Methods:

NUC-1031 was administered on days 1 and 8 with carboplatin on day 1 every 3 weeks for up to six cycles. Four dose cohorts of NUC-1031 (500, 625, and 750 mg/m2) with carboplatin (AUC4 or 5) were investigated. Primary endpoint was recommended phase II combination dose (RP2CD). Secondary endpoints included safety, investigator-assessed objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and pharmacokinetics.

Results:

A total of 25 women with recurrent ovarian cancer, a mean of 3.8 prior lines of chemotherapy, and a median platinum-free interval of 5 months (range: 7–451 days) were enrolled; 15 of 25 (60%) were platinum resistant, 9 (36%) were partially platinum sensitive, and 1 (4%) was platinum sensitive. Of the 23 who were response evaluable, there was 1 confirmed complete response (4%), 5 partial responses (17%), and 8 (35%) stable disease. The ORR was 26% and CBR was 74% across all doses and 100% in the RP2CD cohort. Median PFS was 27.1 weeks. NUC-1031 was stable in the plasma and rapidly generated high intracellular dFdCTP levels that were unaffected by carboplatin.

Conclusions:

NUC-1031 combined with carboplatin is well tolerated in recurrent ovarian cancer. Highest efficacy was observed at the RP2CD of 500 mg/m2 NUC-1031 on days 1 and 8 with AUC5 carboplatin day 1, every 3 weeks for six cycles. The ability to deliver carboplatin at AUC5 and the efficacy of this schedule even in patients with platinum-resistant disease makes this an attractive therapeutic combination.
ZFTA–RELA Dictates Oncogenic Transcriptional Programs to Drive Aggressive Supratentorial Ependymoma
Authors: Arabzade Amir , Zhao Yanhua , Varadharajan Srinidhi , Chen Hsiao-Chi , Jessa Selin , Rivas Bryan , Stuckert Austin J. , Solis Minerva , Kardian Alisha , Tlais Dana , Golbourn Brian J. , Stanton Ann-Catherine J. , Chan Yuen San , Olson Calla , Karlin Kristen L. , Kong Kathleen , Kupp Robert , Hu Baoli , Injac Sarah G. , Ngo Madeline , Wang Peter R. , De León Luz A. , Sahm Felix , Kawauchi Daisuke , Pfister Stefan M. , Lin Charles Y. , Hodges H. Courtney , Singh Irtisha , Westbrook Thomas F. , Chintagumpala Murali M. , Blaney Susan M. , Parsons Donald W. , Pajtler Kristian W. , Agnihotri Sameer , Gilbertson Richard J. , Yi Joanna , Jabado Nada , Kleinman Claudia L. , Bertrand Kelsey C. , Deneen Benjamin , Mack Stephen C.
Published: March 2021

More than 60% of supratentorial ependymomas harbor a ZFTA–RELA (ZRfus) gene fusion (formerly C11orf95–RELA). To study the biology of ZRfus, we developed an autochthonous mouse tumor model using in utero electroporation (IUE) of the embryonic mouse brain. Integrative epigenomic and transcriptomic mapping was performed on IUE-driven ZRfus tumors by CUT&RUN, chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin sequencing, and RNA sequencing and compared with human ZRfus-driven ependymoma. In addition to direct canonical NFκB pathway activation, ZRfus dictates a neoplastic transcriptional program and binds to thousands of unique sites across the genome that are enriched with PLAGL family transcription factor (TF) motifs. ZRfus activates gene expression programs through recruitment of transcriptional coactivators (Brd4, Ep300, Cbp, Pol2) that are amenable to pharmacologic inhibition. Downstream ZRfus target genes converge on developmental programs marked by PLAGL TF proteins, and activate neoplastic programs enriched in Mapk, focal adhesion, and gene imprinting networks.

Significance:

Ependymomas are aggressive brain tumors. Although drivers of supratentorial ependymoma (ZFTA- and YAP1-associated gene fusions) have been discovered, their functions remain unclear. Our study investigates the biology of ZFTA–RELA-driven ependymoma, specifically mechanisms of transcriptional deregulation and direct downstream gene networks that may be leveraged for potential therapeutic testing.

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Effect of Lactic Fermentation Products on Human Epidermal Cell Differentiation, Ceramide Content, and Amino Acid Production
Authors: Otsuka Moe , Tamane Tsuyoshi , Tokudome Yoshihiro
Published: March 2021

Introduction: Lactic fermentation products (LFPs) are thought to affect “good” bacteria in the gut. We previously reported that oral administration of LFPs has beneficial therapeutic effects in a mouse model of atopic dermatitis. However, it is unclear how LFPs affect human epidermal cell differentiation, ceramide (Cer), and amino acid production. Objective: The aim of this study was to determine the effects of LFPs on epidermal cell differentiation, by assessing amino acid and Cer production. Methods: A 3-dimensional cultured human epidermis model and normal human epidermal keratinocytes were used. Cytotoxicity tests were performed using alamar Blue. Transepidermal water loss (TEWL) was used as an index to assess barrier function. Keratin 1 (K1), keratin 5 (K5), keratin 10 (K10), involucrin (INV), calpain 1, and transglutaminase (TGase) (markers of differentiation) and profilaggrin (proFLG) and bleomycin hydrolase (amino acid synthesis-related genes) expression levels were quantified by RT-PCR. In addition, TGase protein levels were measured by Western blotting. The intercellular lipid content of the stratum corneum was measured by high-performance thin-layer chromatography. Amino acids were quantified using an amino acid analyzer. Finally, bound water content in the stratum corneum was measured by differential scanning calorimetry. Results: Cell viability did not change, but TEWL was significantly decreased in the cells treated with LFPs compared with the control cells. Treatment with LFPs significantly increased expression of the late-differentiation markers INV and TGase at the RNA level. Furthermore, TGase protein expression was significantly increased by treatment with LFPs. Treating a 3-dimensional cultured epidermis model with LFPs significantly increased the intercellular lipid content of the stratum corneum and production of the amino acid arginine (Arg). The amount of bound water in the stratum corneum was increased significantly in the LFP application group. Conclusion: Treatment with LFPs promotes human epidermal cell differentiation and increases the intercellular content of the free fatty acid, Chol, Cer [NS], Cer [AS], and Cer [AP]. This may result in improved skin barrier function. The increased amount of Arg observed in keratinocytes may help improve water retention.
Association of Serum Testosterone and Luteinizing Hormone With Blood Pressure and Risk of Cardiovascular Disease in Middle‐Aged and Elderly Men
Authors: Qu Mengyuan , Feng Chenzhao , Wang Xiaotong , Gu Yiqun , Shang Xuejun , Zhou Yuanzhong , Xiong Chengliang , Li Honggang
Published: March 2021

Background

The age‐related decline in testosterone levels is thought to be of great importance for male aging and cardiovascular diseases. However, data are controversial on whether abnormal sex hormones are linked to the presence of cardiovascular diseases and it is also uncertain how blood pressure modifies the association between testosterone levels and major cardiovascular diseases.

Methods and Results

This is a multicenter, population‐based, cross‐sectional study of 6296 men conducted between 2013 and 2016. Basic information and clinical symptoms were obtained by questionnaires. Blood pressure and plasma levels of total testosterone, sex hormone–binding globulin, luteinizing hormone, and free testosterone were determined in men in a multistage random, cluster sampling in 6 provinces of China. There were 5786 Chinese men (mean [SD] age 55.0 [10.1] years) included after exclusion criteria were applied; 37.2% (2150) of them were diagnosed with hypertension. Total testosterone, free testosterone, and sex hormone–binding globulin were inversely associated with the prevalence of hypertension. Age >65 years or body mass index ≥24 negatively impacted the inverse correlation between testosterone levels and hypertension, whereas smoking and family history of hypertension strengthened the correlation. In participants with grade 2 hypertension, total testosterone was positively associated with the presence of stroke, and luteinizing hormone was also positively correlated with cardiovascular and cerebrovascular diseases.

Conclusions

Lower total testosterone could be a promising risk marker for prevalent hypertension. Both low and high levels of testosterone are associated with greater cardiovascular risk. Primary hypogonadism may be a risk marker for major cardiovascular diseases in men with severe hypertension.
Unus Pro Omnibus, Omnes Pro Uno
Authors: Natoli Tommaso
Published: March 2021

Neighbouring States form regional institutions for purposes that they cannot meet singularly, as in case of exceptional events that overwhelm national capacities. Comparing regional organizations endowed with specific Disaster Management (DM) functions provides a suitable analytical lens of this phenomenon, being a means for exploring how fundamental principles like sovereignty or solidarity are differently combined within their legal frameworks. Building on a comparative analysis of two regional models (EU and ASEAN-AHA), the article suggests that the positioning of regional organizations on the sovereignty-solidarity axis is facilitated by an adapted use of the well-known Latin maxim ‘unus pro omnibus, omnes pro uno’. This indicates both dynamics in which the organization is endowed with autonomous capacities of acting in support of members stricken by a catastrophic event, and those regional mechanisms whose functioning depends on the case-by-case involvement of their membership. As will be maintained, whereas these interrelated dynamics coexist in the two organizations analysed, they are differently modelled according to the respective regulatory settings. Yet, common trends in the development of respective institutional functioning can be detected.
Slavery at the Court of the ‘Humanist Prince’ Reexamining Johan Maurits van Nassau-Siegen and his Role in Slavery, Slave Trade and Slave-smuggling in Dutch Brazil
Authors: Monteiro Carolina , Odegard Erik
Published: March 2021

From 1630 until its fall in 1654, the Dutch West India Company maintained a colony in northeastern Brazil where it tried to profit from the cultivation of sugar using enslaved African labor. Count Johan Maurits van Nassau-Siegen served as this colony’s governor-general from 1636 until 1644, this being the most heavily studied period of the colony’s existence. But the role of Johan Maurits in the transatlantic slave trade and enslavement in Brazil is poorly covered by research, with some historians recently arguing that there is ‘no proof’ of any personal involvement. This article presents a clear argument for the personal involvement of Johan Maurits in the slave trade and shows his involvement in slave-smuggling. Understanding the social relations between the count, his court and the Luso-Brazilian elite is in fact simply impossible without bringing in the trade and smuggling of enslaved Africans.
Four new species of Phrynus, Lamarck (Arachnida: Amblypygi) from Mexico
Authors: JOYA DANIEL CHIRIVI
Published: March 2021

Mexico is the country with the largest diversity of the genus Phrynus (Amblypygi: Phrynidae); however, many species could remain hidden due to the conservative morphology of the group. Two of the Mexican species, P. operculatus, and P. jalisco show enough variation, between populations from different localities, to be considered as possible species complexes. The scarce taxonomic information of these species and the few analyses of their variation could cause misidentifications and sub estimation of the diversity. Specimens morphologically similar to P. operculatus from different Mexican localities were analyzed, using characters from the male and female genitals. Four new species are described, presenting illustrations of SEM for the male genitals. Details of the morphologic variation in this group of species are discussed, as well as the usefulness of sexual characters like the size proportions, and sclerotization in the female gonopods, and ornaments in males, to improve the diagnoses of the Mexican Phrynus. The known distribution of P. operculatus is large in comparison with those of the other species, after the result of this research, the possibility that it is a larger species complex is evident, thus, it is necessary to increase the morphologic and genetic population studies in this group.
A new arc-striped species of Corydoras Lacépède, 1803 (Teleostei: Callichthyidae) from the Peruvian Amazon
Authors: BENTLEY REBECCA FRANCES , GRANT STEVEN , TENCATT LUIZ FERNANDO CASERTA
Published: March 2021

A new Corydoras is described from the Blanco and Ucayali river basins in Peru. The new species can be distinguished from its congeners by having the following features: (I) posterior margin of dorsal-fin spine with laminar serrations directed towards the origin of the spine; (II) a long, wide, arched, and continuous black stripe, which runs parallel to the dorsal profile of the body, extending at least from the region below anterior origin of dorsal fin to the anterior half of the ventral caudal-fin lobe; (III) a black stripe transversally crossing the eye, forming the typical mask-like blotch; mask clearly not fused to arched stripe in most specimens; some specimens with mask separated from arched stripe by a thin line around the suture between neurocranium (in the region composed by the posteroventral margin of parieto-supraoccipital plus the posterodorsal margin of the compound pterotic) and first dorsolateral body plate; (IV) posterior margin of pectoral-fin spine with laminar serrations directed towards the origin of the spine; (V) pointed snout, presenting a long mesethmoid, with anterior tip larger than 50% of the entire length of the bone; and (V) ventral surface of trunk covered by small, non-coalescent platelets. A discussion on the possible positive adaptive value of the arc-striped color pattern is also provided.
A new subspecies of giant sengi (Macroscelidea: Rhynchocyon) from coastal Kenya
Authors: AGWANDA BERNARD R. , ROVERO FRANCESCO , LAWSON LUCINDA P. , VERNESI CRISTIANO , AMIN RAJAN
Published: March 2021

A new subspecies of giant sengi or elephant-shrew, first documented in 2008, is described from northern coastal Kenya. All five currently described species and most known subspecies of Rhynchocyon are compared to this new lineage. Molecular analyses using mitochondrial and nuclear markers from the single DNA sample available for the new lineage show differences from other forms and reveal a close relationship with the allopatric golden-rumped sengi R. chrysopygus (0.43% divergence at the 12S mitochondrial locus). This level of 12S divergence is similar to that between other subspecies pairs within Rhynchocyon. Based on three voucher specimens and 843 images from camera traps, the new lineage is similar to R. chrysopygus in the rufous-maroon sides and shoulders but is distinguished by the lack of the golden rump, the presence of jet-black distal rump and thighs, dark dorsal line, and a pronounced nuchal crest of hairs. Though it also shows superficial pelage similarities to two Tanzania species, R. udzungwensis and the dark coastal form of R. cirnei macrurus, the new form has differences in pelage coloration that are clearly diagnosable from all other taxa. This new lineage has an allopatric distribution to all known Rhynchocyon taxa, with the closest congener being R. chrysopygus located 140 km apart. We estimate a potential range size for the new taxon of ~1980 km2 in the Boni and Dodori National Reserves with habitat consisting of mixed thickets and dry forests. Because of its close genetic relationship with R. chrysopygus, its allopatric distribution, and divergent coloration, the new subspecies is designated Rhynchocyon chrysopygus mandelai. The previously described populations of R. chrysopygus from southern coastal Kenya are now designated R. chrysopygus chrysopygus. As the current severe political insecurity in the area threatens the new taxon, we hope that its description will help establish immediate conservation priorities and action for the subspecies and its habitat.
Tadpole of Nyctimantis galeata (Anura: Hylidae: Lophyohylini), a narrow endemic casque-headed frog from Bahia, Brazil
Authors: MAGALHÃES FELIPE DE MEDEIROS , MARQUES RICARDO , DOS SANTOS DANIELA FONSECA , DE MAGALHÃES RAFAEL FÉLIX , PEZZUTI TIAGO LEITE
Published: March 2021

Nyctimantis galeata (Pombal, Menezes, Fontes, Nunes, Rocha & Van Sluys) is a casque-headed frog member of the Lophyohylini tribe (Blotto et al. 2020), narrow-endemic to the municipality of Morro do Chapéu, Bahia state, Brazil (Pombal et al. 2012). This species was initially described as sister of Corythomantis greeningi Boulenger based on shared osteological autapomorphies within Hylidae (see Faivovich et al. 2005; Pombal et al. 2012). However, in the most recent molecular phylogenetic analysis of Lophyohylini, Blotto et al. (2020) redefined the genus Nyctimantis to accommodate species from the former genus Aparasphenodon, Argenteohyla and “Corythomantis galeata” (as initially described; Pombal et al. 2012). Currently, the genus Nyctimantis comprises seven species: N. arapapa (Pimenta, Napoli & Haddad), N. bokermanni (Pombal), N. brunoi (Miranda-Ribeiro), N. galeata, N. pomba (Assis, Santana, Silva, Quintela & Feio), N. rugiceps Boulenger, and N. siemersi (Mertens). Among these, N. arapapa (Lourenço-de-Moraes et al. 2013), N. brunoi (Wogel et al. 2006) and N. siemersi (Céspedez 2000; Cajade et al. 2010) have their tadpoles described, while oral cavity anatomy was only reported for those of N. brunoi and N. siemersi (Wogel et al. 2006; Cajade et al. 2010). Considering that larval morphology generally provides reliable information for anuran systematic and taxonomic studies (Wassersug 1980; McDiarmid & Altig 1999; Haas 2003), a formal comparison of these larvae might highlight additional non-molecular evidence that support them as congeners (Blotto et al. 2020). Herein, we describe the external morphology and oral cavity anatomy of tadpoles of N. galeata and compare it with those of related species.
WRF Precipitation Performance and Predictability for Systematically Varied Parameterizations over Complex Terrain
Authors: Jeworrek Julia , West Gregory , Stull Roland
Published: March 2021

Physics parameterizations in the Weather Research and Forecasting (WRF) Model are systematically varied to investigate precipitation forecast performance over the complex terrain of southwest British Columbia (BC). Comparing a full year of modeling data from over 100 WRF configurations to station observations reveals sensitivities of precipitation intensity, season, location, grid resolution, and accumulation window. The choice of cumulus and microphysics parameterizations is most important. The WSM5 microphysics scheme yields competitive verification scores when compared to more sophisticated and computationally expensive parameterizations. Although the scale-aware Grell–Freitas cumulus parameterization performs better for summertime convective precipitation, the conventional Kain–Fritsch parameterization better simulates wintertime frontal precipitation, which contributes to the majority of the annual precipitation in southwest BC. Finer grid spacings have lower relative biases and a more realistic spread in precipitation intensity distribution, yet higher relative standard deviations of their errors—they produce finer spatial differences and local extrema. Finer resolutions produce the best fraction of correct-to-incorrect forecasts across all precipitation intensities, whereas the coarser 27-km domain yields the highest hit rates and equitable threat scores. Verification metrics improve greatly with longer accumulation windows—hourly precipitation values are prone to double-penalty issues, while longer accumulation windows compensate for timing errors but lose information about short-term precipitation intensities. This study provides insights regarding WRF precipitation performance in complex terrain across a wide variety of configurations, using metrics important to a range of end users.