bluuebunny/crossref_metadata_2025 huggingface dataset:
One Hundred Years of Hybrid Necrosis: Hybrid Autoimmunity as a Window into the Mechanisms and Evolution of Plant–Pathogen Interactions
Authors: Li Lei , Weigel Detlef
Published: May 2021

Hybrid necrosis in plants refers to a genetic autoimmunity syndrome in the progeny of interspecific or intraspecific crosses. Although the phenomenon was first documented in 1920, it has been unequivocally linked to autoimmunity only recently, with the discovery of the underlying genetic and biochemical mechanisms. The most common causal loci encode immune receptors, which are known to differ within and between species. One mechanism can be explained by the guard hypothesis, in which a guard protein, often a nucleotide-binding site–leucine-rich repeat protein, is activated by interaction with a plant protein that mimics standard guardees modified by pathogen effector proteins. Another surprising mechanism is the formation of inappropriately active immune receptor complexes. In this review, we summarize our current knowledge of hybrid necrosis and discuss how its study is not only informing the understanding of immune gene evolution but also revealing new aspects of plant immune signaling.
The “Burden” of Oppositional Culture Among Black Youth in America
Authors: Tyson Karolyn , Lewis Amanda E.
Published: May 2021

For decades, any scholarly conversation about the academic achievement of youth of color, and especially Black youth, required at least a nod to the widely discussed topic of oppositional culture. In this review, we explore whether Black youth are burdened by a peer culture oppositional to dominant institutions and achievement norms. We begin by focusing on recent research addressing oppositional culture and find little to no support for the main propositions of this theory, even as the ideas remain popular in academic and lay circles. We then turn our attention to other recent research on Black youth's educational experiences and find evidence that these youth might be better understood as burdened by structural, institutional, and interpersonal racism that they and other minoritized students face in school. We conclude by offering suggestions for research moving forward, arguing that it is time to expand the conversation within sociology on Black youth.
Numerical Investigation of Multistage Fractured Horizontal Wells considering Multiphase Flow and Geomechanical Effects
Authors: Li Jun , Liu Yuetian , Ma Kecong
Published: May 2021

Hydraulic fracturing is a key technology in unconventional reservoir production, yet many simulators only consider the single-phase flow of shale gas, ignoring the two-phase flow process caused by the retained fracturing fluid in the early stage of production. In this study, a three-dimensional fluid–gas–solid coupling reservoir model is proposed, and the governing equations which involve the early injection water phenomenon and stress-sensitive characteristics of shale gas reservoirs are established. The finite element–finite difference method was used for discretisation of stress and strain equations and the equations of flow balances. Further, a sensitivity analysis was conducted to analyse fracture deformation changes in the production. Fracture characteristics under different rock mechanics coefficients were simulated, and the influence of rock mechanics parameters on productivity was further characterised. The stimulated reservoir volume zone permeability could determine the retrofitting effect, the permeability increased from 0.02 to 0.1 mD, and cumulative gas production increased from 18.08 to 26.42 million m3, thus showing an increase of 8.34 million m3, or 46%. The effect of Young’s modulus on the yield was smaller than Poisson’s ratio and the width and length of the fractures. Production was most sensitive to the length of the fractures. The length of the fracture increased from 200 to 400 m, and the cumulative gas production increased from 26.44 to 38.34 million m3, showing an increase of 11.9 million m3, or 45%. This study deepens the understanding of the production process of shale gas reservoirs and has significance for the fluid–gas–solid coupling of shale gas reservoirs.
In Vivo Corrosion Behavior of Biodegradable Magnesium Alloy by MAF Treatment
Authors: Gao Xinzhe , Dai Chun Yu , Jia Qi , Zhai ChuanYao , Shi HaoYu , Yang Yifan , Zhao Bing Cheng , Cai HongXin , Lee Eui-Seok , Jiang Heng Bo
Published: May 2021

Coating treatment plays an irreplaceable role in propelling the clinical application of magnesium alloys. This experiment was designed in order to observe the anticorrosion behavior of magnesium fluoride coating in rats. The MgF2 layer was prepared on the surface of AZ31 magnesium alloy in saturated NH4HF2 solution by microarc fluorination (MAF) at 190 V. The cross-sectional SEM, EDS, and XRD analysis indicated that the alloy surface was covered with MgF2. Meanwhile, SEM observation was used to compare the magnesium alloy samples before and after treatment, and it was found that the samples after coating were flatter and smoother. Two sets of experiments were carried out with the subjects, 6-week-old male rats. So that the untreated AZ31 samples and the microarc fluorinated AZ31 samples could be buried under the muscle layer individually. The volume changes and surface morphology of the corroded samples were monitored dynamically using micro-CT over a 16-week period in vivo. Comparison of results between the two sets of samples presented that the corrosion of the microarc fluoridated samples was much slower than that of the untreated ones. The MAF coating was shown to be effective in controlling the corrosion rate and progression of the magnesium alloy.
Repulsive Guidance Molecule‐a and Central Nervous System Diseases
Authors: Tang Jinhua , Zeng Xiaopeng , Li Hang , Ju Lu , Feng Jinzhou , Yang Jun
Published: May 2021

Repulsive guidance molecule‐a (RGMa) is a member of glycosylphosphatidylinositol‐ (GPI‐) anchored protein family, which has axon guidance function and is widely involved in the development and pathological processes of the central nervous system (CNS). On the one hand, the binding of RGMa and its receptor Neogenin can regulate axonal guidance, differentiation of neural stem cells into neurons, and the survival of these cells; on the other hand, RGMa can inhibit functional recovery of CNS by inhibiting axonal growth. A number of studies have shown that RGMa may be involved in the pathogenesis of CNS diseases, such as multiple sclerosis, neuromyelitis optica spectrum diseases, cerebral infarction, spinal cord injury, Parkinson’s disease, and epilepsy. Targeting RGMa can enhance the functional recovery of CNS, so it may become a promising target for the treatment of CNS diseases. This article will comprehensively review the research progression of RGMa in various CNS diseases up to date.
Study of the Phytochemical Composition, the Antioxidant and the Anti-Inflammatory Effects of Two Sub-Saharan Plants: Piliostigma reticulatum and Piliostigma thonningii
Authors: Boualam K. , Ndiaye B. , Harhar H. , Tabyaoui M. , Ayessou N. , Taghzouti K.
Published: May 2021

The aim of this study is to perform phytochemical screening of the leaves of Piliostigma reticulatum and Piliostigma thonningii, to determine the phenolic, flavonoids, tannins, and sugars content in their methanolic extracts, evaluate their antioxidant activity using the DPPH and the ABTS tests, and test their anti-inflammatory effect in vitro using the heat-induced albumin denaturation inhibition method. Phytochemical screening revealed the presence of polyphenols and alkaloids in the leaves of both plants. Yields of the extracts in this study ranged from 7% to 18% for P. reticulatum and 4% to 16% for P. thonningii. The phenolic content in the methanolic extract of P. reticulatum is 74.66 ± 1.76 μg GAE/mL, which is significantly higher than that of P. thonningii (56.54 ± 1.24 μg GAE/mL). Both plants showed good antioxidant activity. In fact, for the DPPH test, the IC50 value is 8.88 ± 0.11 μg/mL for P. reticulatum and 17.64 ± 0.68 μg/mL for P. thonningii. For the ABTS assay, the IC50 values of the two plants are, respectively, 9.78 ± 1.83 μg/mL and 13.47 ± 2.62 μg/ml, statistically comparable and significantly higher than the IC50 of the standard 30.76 ± 0.18 μg/ml. Leaf extracts from both plants were effective against heat-induced denaturation of albumin. The activity of P. reticulatum is indeed comparable to that of the standard with an IC50 value of 121.43 ± 1.55 μg/mL and higher than that of P. thonningii with an IC50 value of 170.15 ± 1.09 μg/mL. These results show that both plants exhibit significant antioxidant and anti-inflammatory activities. Therefore, their chemical compounds could have potential applications as antioxidant and anti-inflammatory drugs.
[Retracted] Experimental Study on the Correlation between miRNA‐373 and HIF‐1α, MMP‐9, and VEGF in the Development of HIE
Authors: Liu Chun-Yang , Al-Ward Hisham , Ngaffo Mekontso Francine , Liu Ning , Zeng Hui-Qin , Liu Min , Yu Zi-Rui , Zhang Lin , Han Yu-Chun , Xu Hui
Published: May 2021

Introduction. Microribonucleic acids (miRNAs) have short (approximately 18 to 25) nucleotides and are evolutionarily conserved and endogenously expressed RNAs belonging to a family of noncoding RNA molecules. miRNA‐373 regulates cell proliferation, migration, apoptosis, invasion, and repairing damaged DNA after hypoxia stress. Neonatal hypoxic–ischemic encephalopathy (HIE) refers to perinatal asphyxia caused by partial or complete hypoxia, reduced or suspended cerebral blood flow, and fetal or neonatal brain damage. We aim to investigate the relationship between miRNA‐373 and HIF‐1α, between miRNA‐373 MMP‐9, and between miRNA‐373 VEGF in the occurrence and development of HIE. Methods. Human (children) samples were divided into four groups (n = 15 in each group) according to HIE severity. The patient group was divided into middle, moderate, and severe HIE groups. The control group included healthy children or children with nonneurological diseases. The expressions of miRNA‐373, HIF‐1α, MMP‐9, and VEGF were assayed in the serum samples. Results. Our study showed a strong relationship between miRNA‐373 and HIF‐1α, between miRNA‐373 and MMP‐9, and between miRNA‐373 and VEGF. The expression levels of miRNA‐373, HIF‐1α, MMP‐9, and VEGF in the HIE groups were much higher than those of the control group. Conclusion. The increased change in miRNA‐373 expression has a certain diagnostic significance on neonatal HIE. In the occurrence and development of HIE, miRNA‐373 is positively correlated with HIF‐1α, MMP‐9, and VEGF.
The Association between Gly460Trp-Polymorphism of Alpha-Adducin 1 Gene (ADD1) and Arterial Hypertension Development in Ukrainian Population
Authors: Yermolenko Svitlana , Chumachenko Yaroslav , Orlovskyi Viktor , Moiseyenko Irina , Orlovskyi Oleksandr
Published: May 2021

Arterial hypertension (AH) belongs to the diseases with genetic predisposition that determines the necessity of research on the genetic component’s influence on this disease development. It is suggested that one of the salt-sensitive arterial hypertension potential markers may be the alpha-adducin gene because its protein product is involved in the ion transport regulation in the renal epithelium. Thus, the aim of the study was to investigate the association between ADD1 Gly460Trp-polymorphism and the AH development risk among patients with different risk factors in the Ukrainian population. The study included 232 Ukrainians: 120 patients with diagnosed arterial hypertension and 112 practically healthy individuals. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used for ADD1 Gly460Trp-polymorphism genotyping. The ADD1 Gly460Trp-polymorphic locus is an important predictor of arterial hypertension development in the Ukrainian population, but other nongenetic factors should be considered in further studies.
Effects of Nonpharmacological Interventions on Balance Function in Patients with Osteoporosis or Osteopenia: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Zhu Lu , Wu Wenzhong , Chen Ming , Xu Daoming , Xu Huaning , Liu Lanying , Liu Jing , Zhu Zequan
Published: May 2021

Objective. To evaluate the clinical efficacy of nonpharmacological interventions in improving balance function of patients with osteoporosis or osteopenia using network meta-analysis (NMA). Methods. We searched seven databases (PubMed, the Cochrane Library, Embase, CKNI, Wanfang Data, VIP, and CBM) for relevant randomized controlled trials (RCTs) up to August 31, 2020. Berg Balance Scale (BBS) and Time Up and Go Test (TUGT) were used as outcome measures. Two researchers independently screened studies, collected data from the studies, and estimated risk of study bias. Divergence in the evaluation process was settled by consulting a third researcher. We used Stata 15.1 software for network meta-analysis (NMA). Results. We identified 10 eligible RCTs, with a total of 737 patients and four intervention methods, including traditional Chinese medicine (TCM) exercises, pulsed electromagnetic fields (PEMFs), strength training, and balance and strength training. The results revealed that all nonpharmacological interventions could improve balance function, but the effect of balance and strength training was better than other interventions. Conclusion. Exercise can significantly improve the balance function of patients with osteoporosis and osteopenia, and balance combined with strength training has the best effect, followed by TCM exercises.
Shielding Design and Dose Evaluation for HTR-PM Fuel Transport Pipelines by QAD-CGA Program
Authors: Fang Sheng , Cao Jianzhu , Li Wenqian , Luo Chen , Yao Feng , Li Xiaofan , Li Kai
Published: May 2021

The spherical fuel elements are adopted in the high-temperature gas-cooled reactor pebble-module (HTR-PM). The fuel elements will be discharged continuously from the reactor core and transported into the fuel transport pipelines during the reactor operation, leading to spatially varying dose outside the pipeline. In this case, the dose evaluation faces two major challenges, including dynamic source terms and pipelines with varying lengths and shapes. This study tries to handle these challenges for HTR-PM through comprehensive calculations using the QAD-CGA program and to design the corresponding shielding of the pipeline. During the calculation, it is assumed that a spherical fuel element stays in different positions of the pipelines in turn, and the corresponding dose contributions were calculated. By integrating the dose contributions at different positions, the dose at the points of interest can be obtained. The total dose is further determined according to the assumed fuel elements transport speed of 5 m/s and total 6000 fuel elements transportation per day. Two types of fuel transport pipelines and two source terms were considered, i.e., the spent fuel element transport pipelines with corresponding spent fuel source term and the different burn-up fuel element transport pipelines with the average burn-up fuel source term. Doses at different points of interest were calculated with no shielding scenario and with lead shielding of different thicknesses scenario. To evaluate the shielding effect, the dose limit of the orange radiation zone of HTR-PM and the radiation damage thresholds from NCRP report No.51 were both adopted. The calculated results show that, for pipelines that transport the spent fuel, a 4 cm lead shielding will be enough. And for pipelines that transport fuel elements with different burn-up, a 5 cm lead shielding will be added. The method and results can provide valuable reference for other work of HTR-PM.
Effect of LPS on Cytokine Secretion from Peripheral Blood Monocytes in Juvenile Idiopathic Arthritis-Associated Uveitis Patients with Positive Antinuclear Antibody
Authors: Wang Jing , Wu Huiru , Liu Xinli , Jia Huiyu , Lu Hong
Published: May 2021

Objectives. Antinuclear antibody (ANA) positivity is a key finding in JIA-associated uveitis (JIAU), but there are quite a few patients with negative ANA. There is no relevant report on the difference of their clinical manifestations. Previous animal model studies have found that the occurrence of uveitis is related to macrophage activation. In this article, our goal is to investigate changes in the morphology and cytokines of peripheral blood mononuclear cells (PBMCs) in uveitis patients testing positive or negative for ANAs after lipopolysaccharide (LPS) stimulation. Methods. A total of 30 patients were included in this study (10 in each group). They were divided into three groups (the ANA-positive [ANA+] group, ANA-negative [ANA-] group, and control group). There were ten patients (6 females and 4 males) in each group. Peripheral venous blood was collected into a heparinized tube, and PBMCs were isolated as soon as possible by the Ficoll-Hypaque density gradient separation method. Isolated cells were mixed with RPMI-1640 medium, and the cell concentration was adjusted to ensure that each patient had the same number of cells entering the study. After putting the extracted PBMC into the culture plate, LPS was added carefully to the plate. The cell culture supernatants were collected at 0 h, 3 h, 6 h, 12 h, and 24 h after LPS stimulation to detect the concentrations of IL-6, IL-1, TNF-α, and IL-10. Immunofluorescence was used to discover the deformation of macrophages after LPS stimulation. Results. The newly isolated cells were approximately round. 6 h after LPS stimulation, the ratio of noncircular cells/circular cells was the highest in the ANA+ group. Unlike IL-10 that has been rising during the observation period, IL-6, IL-1, and TNF-α peaked at 6 h after LPS stimulation. Conclusion. With LPS motivation, cytokines in the ANA+ group increased the most violently.
Diagenetic Modifications and Reservoir Heterogeneity Associated with Magmatic Intrusions in the Devonian Khyber Limestone, Peshawar Basin, NW Pakistan
Authors: Shah Mumtaz M. , Afridi Saifullah , Khan Emad U. , Rahim Hamad Ur , Mustafa Muhammad R.
Published: May 2021

In the present study, an attempt has been made to establish the relationship between diagenetic alterations resulting from magmatic intrusions and their impact on the reservoir properties of the Devonian Khyber Limestone (NW Pakistan). Field observations, petrographic studies, mineralogical analyses, porosity-permeability data, and computed tomography were used to better understand the diagenetic history and petrophysical property evolution. Numerous dolerite intrusions are present in the studied carbonate successions, where the host limestone was altered to dolomite and marble, and fractures and faults developed due to the upwelling of the magmatic/hydrothermal fluids along pathways. Petrographic studies show an early phase of coarse crystalline saddle dolomite (Dol. I), which resulted from Mg-rich hydrothermal fluids originated from the dolerite dykes. Coarse crystalline marble formed due to contact metamorphism at the time of dolerite emplacement. The second phase of dolomitisation (Dol. II) postdates the igneous intrusions and was followed by dedolomitisation, dissolution, and cementation by meteoric calcite. Stable isotope studies likewise confirm two distinct dolomite phases. Dol. I exhibits more depleted δ18O (-15.8 to -9.1‰ V-PDB) and nondepleted δ13C (-2.05 to +1.85‰ V-PDB), whereas Dol. II shows a relatively narrow range of depleted δ18O (-13.9 to -13.8‰) signatures and nondepleted δ13C (+1.58 to +1.89‰ V-PDB). Dolomitic marble shows a marked depletion in δ18O and δ13C (-13.7 to -8.5‰ and -2.3 to 1.95‰, respectively). The initial phase of dolomitisation (Dol. I) did not alter porosity (5.4-6.6%) and permeability (0.0-0.1 mD) with respect to the unaltered limestone (5.6-6.9%; 0.1-0.2 mD). Contact metamorphism resulted in a decrease in porosity and permeability (3.3-4.7%; 0.1 mD). In contrast, an increase in porosity and permeability in Dol. II (7.7-10.5%; 0.8-2.5 mD) and dolomitic marble (6.6-14.7%; 8.2-13.3 mD) is linked to intercrystalline porosity and retainment of fracture porosity in dolomitic marble. Late-stage dissolution and dedolomitization also positively affected the reservoir properties of the studied successions. In conclusion, the aforementioned results reveal the impact of various diagenetic processes resulting from magmatic emplacement and their consequent reservoir heterogeneity.
Numerical Simulation of Tandem Shaped Charge Penetrating Armored Target under Explosive Loading
Authors: Yin Jianping , Duan Conghui , Han Yangyang , Wang Zhijun , Chen Jie
Published: May 2021

Tandem shaped charge is one of the hotspots in the research of antiarmor ammunition at present, but because of the shortcoming that the front‐stage jet penetrates and detonates ERA (Explosive Reactive Armor), then it will affect the rear‐stage jet to penetrate the main armor. Our research team proposes that the front charge of the tandem shaped charge can be designed as a low‐density material charge liner so that the front‐stage low‐density jet can penetrate a small hole in the reactive armor without detonating. The rear‐stage main charge forms a main jet through the small hole to penetrate the main armor. In this article, the damage of tandem shaped charge to armored target is studied when copper and new modified PTFE (polytetrafluoroethylene) materials are used as front‐stage charge liner, and the numerical simulation results are verified by experiments. The numerical results show that the Cu (copper) jet formed by tandem shaped charge of double‐copper material has strong impact performance. The interlayer explosive in reactive armor is detonated in the process of penetrating reaction armor, which weakens the penetration ability of the main rear‐jet. However, the interlayer explosive in the reactive armor is not detonated during the penetration of the double‐material tandem shaped charge. The front‐stage modified PTFE jet and the rear‐stage main jet are not affected by the explosion loading before penetrating the main armor. The experimental results show that the double‐material tandem shaped charge overcomes the shortcoming of the influence of the front‐stage explosion, and the penetration depth of the main armor reaches 703 mm, which is 14.3% higher than the penetration ability of the double‐copper tandem shaped charge, which is basically consistent with the numerical simulation results. It provides a reference for improving the damage ability of tandem shaped charge to armored target.
Agitation and Sugar Craving Related to Epilepsy Seizure
Authors: Hameed Rania Adel , Aghdam Mohammad Reza F.
Published: May 2021

Introduction. Epilepsy is a chronic central nervous system disorder characterized by the recurrence of unprovoked seizures and can affect people of all ages. Seizure symptoms can vary widely in patients. Many papers have been published about agitation and epileptic seizures, but almost nothing about sugar cravings and agitation related to epilepsy. The purpose of this case report is to shed light on possibly a hidden symptom within the epilepsy field, in fact sugar cravings. Case presentation. A 12-year-old boy was referred to the children and adolescent psychiatric outpatient clinic with suspicion of ADHD. The boy has struggled with anxiety, concentration, and impulsivity. Because of intense agitation and sugar cravings, the patient was referred to EEG. The EEG shows pathological activity with bilatero-temporal to central epileptiform activity, not synchronized. After pathological EEG findings, the patient started treatment with Lamotrigine. Great improvement when it comes to agitation, moodiness, and reduction of sugar craving after starting with Lamotrigine. Conclusion. We consider inexplicable behavior or symptoms such as agitation and sugar craving may be related to epilepsy seizure. Therefore, it is important that these patients should be examined more closely with EEG to confirm or deny epilepsy.
Bilateral Knee Dislocations Treated with Acute, Single-Stage Multiligament Reconstructions
Authors: Imbergamo Casey , Brzezinski Andrzej , Smith Tiffany , Buckley Patrick S. , Swan Kenneth G.
Published: May 2021

Bilateral knee dislocations are exceedingly rare in orthopaedics. Managing these injuries presents a difficult task given their high complication rate and guarded prognosis. We report the case of a 21-year-old male who presented to our institution with bilateral knee dislocations sustained in a motor vehicle collision. The patient subsequently underwent multiligament knee reconstruction surgeries for each knee at one and three weeks following the initial injury. At one-year follow-up, the patient has achieved a successful outcome and has returned to regular activities which include hiking and exercising at the gym.
The Lomax‐Claim Model: Bivariate Extension and Applications to Financial Data
Authors: Zhao Jin , Faqiri Humaira , Ahmad Zubair , Emam Walid , Yusuf M. , Sharawy A. M.
Published: May 2021

The uses of statistical distributions for modeling real phenomena of nature have received considerable attention in the literature. The recent studies have pointed out the potential of statistical distributions in modeling data in applied sciences, particularly in financial sciences. Among them, the two‐parameter Lomax distribution is one of the prominent models that can be used quite effectively for modeling data in management sciences, banking, finance, and actuarial sciences, among others. In the present article, we introduce a new three‐parameter extension of the Lomax distribution via using a class of claim distributions. The new model may be called the Lomax‐Claim distribution. The parameters of the Lomax‐Claim model are estimated using the maximum likelihood estimation method. The behaviors of the maximum likelihood estimators are examined by conducting a brief Monte Carlo study. The potentiality and applicability of the Lomax claim model are illustrated by analyzing a dataset taken from financial sciences representing the vehicle insurance loss data. For this dataset, the proposed model is compared with the Lomax, power Lomax, transmuted Lomax, and exponentiated Lomax distributions. To show the best fit of the competing distributions, we consider certain analytical tools such as the Anderson–Darling test statistic, Cramer–Von Mises test statistic, and Kolmogorov–Smirnov test statistic. Based on these analytical measures, we observed that the new model outperforms the competitive models. Furthermore, a bivariate extension of the proposed model called the Farlie–Gumble–Morgenstern bivariate Lomax‐Claim distribution is also introduced, and different shapes for the density function are plotted. An application of the bivariate model to GDP and export of goods and services is provided.
Study on Automotive Back Door Panel Injection Molding Process Simulation and Process Parameter Optimization
Authors: Wang Guoqing , Wang Youmin , Yang Deyu
Published: May 2021

A plastic back door car panel was considered as the research object. In order to obtain optimal injection molding simulation parameters, Moldflow2018 is used to simulate injection molding process of plastic back door car panel. Orthogonal experiment is conducted to analyze the influence of injection process parameters on the evaluation index. Melt temperature, mold temperature, cooling time, packing pressure, and packing time are selected as process parameters. Warpage and volumetric shrinkage are taken as evaluation indicators. Test groups are designed to obtain data, and range analysis method is employed to analyze warpage and volumetric shrinkage. Warpage range analysis shows that optimal warpage is 9.3 mm for volumetric shrinkage rate of 14.3%. Range analysis of volumetric shrinkage rate indicates that the best warpage is 8.3 mm for the corresponding volumetric shrinkage rate of 15.05%. A comprehensive evaluation index is established using the gray relational analysis. This analysis shows that warpage is 8.3 mm and volumetric shrinkage rate is 14.2%. Taguchi method is employed to obtain signal‐to‐noise ratio, while range and variance methods are used for the analysis. Optimal warpage is obtained as 8.2 mm, while the volume shrinkage rate is 10.3%. For a single evaluation index warpage, least squares method and artificial fish swarm algorithm are used to find the optimal parameter combination. Moldflow2018 is employed for simulation verification, and minimum warpage is obtained as 6.405 mm.
Semi‐Analytical Solutions for the Diffusive Kaldor–Kalecki Business Cycle Model with a Time Delay for Gross Product and Capital Stock
Authors: Alfifi H. Y.
Published: May 2021

This paper discusses the stability and Hopf bifurcation analysis of the diffusive Kaldor–Kalecki model with a delay included in both gross product and capital stock functions. The reaction‐diffusion domain is considered, and the Galerkin analytical method is used to derive the system of ordinary differential equations. The methodology used to determine the Hopf bifurcation points is discussed in detail. Furthermore, full diagrams of the Hopf bifurcation regions considered in the stability analysis are shown, and some numerical simulations of the limit cycle are used to confirm the theoretical outcomes. The delay investment parameter and diffusion coefficient can have great impacts on the Hopf bifurcations and stability of the business cycle model. The investment parameters for the gross product and capital stock as well as the adjustment coefficient of the production market are also studied. These parameters can cause instability in, and the stabilization of, the business cycle model. In addition, we point out that, as the delay investment parameter increases, the Hopf bifurcation points for the diffusion coefficient values decrease considerably. When the delay investment parameter has a very small value, the solution of the business cycle model tends to become steady.
Phase I–II Open-Label Multicenter Study of Palbociclib + Vemurafenib in BRAFV600MUT Metastatic Melanoma Patients: Uncovering CHEK2 as a Major Response Mechanism
Authors: Louveau Baptiste , Resche-Rigon Matthieu , Lesimple Thierry , Da Meda Laetitia , Pracht Marc , Baroudjian Barouyr , Delyon Julie , Amini-Adle Mona , Dutriaux Caroline , Reger de Moura Coralie , Sadoux Aurélie , Jouenne Fanélie , Ghrieb Zineb , Vilquin Paul , Bouton Didier , Tibi Annick , Huguet Samuel , Rezai Keyvan , Battistella Maxime , Mourah Samia , Lebbe Céleste
Published: May 2021

Purpose:

In BRAFV600MUT metastatic melanoma, cyclin D–CDK4/6–INK4–Rb pathway alterations are involved in resistance to MAPK inhibitors, suggesting a clinical benefit of cyclin-dependent kinase 4 (CDK4) inhibitors. In this phase I–II study, we aimed to establish the MTD of palbociclib when added to vemurafenib.

Patients and Methods:

Patients with BRAFV600E/KMUT metastatic melanoma harboring CDKN2A loss and RB1 expression were included and stratified into two groups according to previous BRAF inhibitor treatment (no:strata 1; yes:strata 2). Treatment comprised palbociclib once daily for 14 days followed by a 7-day break + continuous dosing of vemurafenib. The primary endpoint was the occurrence of dose-limiting toxicity (DLT), and the secondary endpoints included the best response, survival, pharmacokinetics, and tumor molecular profiling.

Results:

Eighteen patients were enrolled, with 15 in strata 2. Characteristics at inclusion were American Joint Committee on Cancer stage IVM1c (N = 16; 88.9%), high lactate dehydrogenase (N = 9; 50.0%), and median number of previous treatments of 2. One and 5 patients experienced DLT in strata 1 and 2, respectively, defining the MTD at palbociclib 25 mg and vemurafenib 960 mg in strata 2. No significant evidence for drug–drug interactions was highlighted. The median progression-free survival was 2.8 months, and 5 (27.8%) patients showed a clinical response. The baseline differential mRNA expression analysis and in vitro data revealed the role of CHEK2 in the response to palbociclib.

Conclusions:

Although the combination of palbociclib + fixed-dose vemurafenib did not allow an increased palbociclib dosage above 25 mg, a significant clinical benefit was achieved in pretreated patients with melanoma. An association between the transcriptomic data and clinical response was highlighted.
Deep Learning for Fully Automated Prediction of Overall Survival in Patients with Oropharyngeal Cancer Using FDG-PET Imaging
Authors: Cheng Nai-Ming , Yao Jiawen , Cai Jinzheng , Ye Xianghua , Zhao Shilin , Zhao Kui , Zhou Wenlan , Nogues Isabella , Huo Yuankai , Liao Chun-Ta , Wang Hung-Ming , Lin Chien-Yu , Lee Li-Yu , Xiao Jing , Lu Le , Zhang Ling , Yen Tzu-Chen
Published: May 2021

Purpose:

Accurate prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is crucial. We developed an objective and robust deep learning–based fully-automated tool called the DeepPET-OPSCC biomarker for predicting overall survival (OS) in OPSCC using [18F]fluorodeoxyglucose (FDG)-PET imaging.

Experimental Design:

The DeepPET-OPSCC prediction model was built and tested internally on a discovery cohort (n = 268) by integrating five convolutional neural network models for volumetric segmentation and ten models for OS prognostication. Two external test cohorts were enrolled—the first based on the Cancer Imaging Archive (TCIA) database (n = 353) and the second being a clinical deployment cohort (n = 31)—to assess the DeepPET-OPSCC performance and goodness of fit.

Results:

After adjustment for potential confounders, DeepPET-OPSCC was found to be an independent predictor of OS in both discovery and TCIA test cohorts [HR = 2.07; 95% confidence interval (CI), 1.31–3.28 and HR = 2.39; 95% CI, 1.38–4.16; both P = 0.002]. The tool also revealed good predictive performance, with a c-index of 0.707 (95% CI, 0.658–0.757) in the discovery cohort, 0.689 (95% CI, 0.621–0.757) in the TCIA test cohort, and 0.787 (95% CI, 0.675–0.899) in the clinical deployment test cohort; the average time taken was 2 minutes for calculation per exam. The integrated nomogram of DeepPET-OPSCC and clinical risk factors significantly outperformed the clinical model [AUC at 5 years: 0.801 (95% CI, 0.727–0.874) vs. 0.749 (95% CI, 0.649–0.842); P = 0.031] in the TCIA test cohort.

Conclusions:

DeepPET-OPSCC achieved an accurate OS prediction in patients with OPSCC and enabled an objective, unbiased, and rapid assessment for OPSCC prognostication.
Preclinical Development and First-in-Human Study of KA2507, a Selective and Potent Inhibitor of Histone Deacetylase 6, for Patients with Refractory Solid Tumors
Authors: Tsimberidou Apostolia M. , Beer Philip A. , Cartwright Carrie A. , Haymaker Cara , Vo Henry H. , Kiany Simin , Cecil Alexander R.L. , Dow James , Haque Kemal , Silva Franck A. , Coe Lucy , Berryman Helen , Bone Elisabeth A. , Nogueras-Gonzalez Graciela M. , Vining David , McElwaine-Johnn Hilary , Wistuba Ignacio I.
Published: May 2021

Purpose:

Inhibition of histone deacetylase 6 (HDAC6) is predicted to deliver both direct antitumor activity and modulation of the antitumor immune response. This study describes the development of a novel HDAC6 inhibitor.

Patients and Methods:

KA2507 was characterized in HDAC biochemical and cellular target engagement assays and in preclinical efficacy models of melanoma and colorectal cancer. In a phase I study, KA2507 was administered orally using a 3+3 dose-escalation design (NCT03008018).

Results:

KA2507 is a potent and selective inhibitor of HDAC6 (biochemical IC50 = 2.5 nmol/L). Preclinical models demonstrated antitumor efficacy in syngeneic tumor-bearing mice, with translational studies highlighting modulation of the antitumor immune response. Twenty patients were treated in a phase I study. KA2507 was well tolerated; dose-limiting toxicity was not observed up to the maximum dose administered. Pharmacokinetic profiling supported twice-daily oral dosing. Pharmacodynamic analysis demonstrated selective HDAC6 target engagement in peripheral blood cells, free from off-target class I HDAC activity. Stable disease was the best clinical response (7 patients). Three of these patients (adenoid cystic carcinoma, n = 2; rectal adenocarcinoma, n = 1) had prolonged disease stabilization that lasted for 16.4, 12.6, and 9.0 months, respectively.

Conclusions:

KA2507 is a potent and selective inhibitor of HDAC6 showing antitumor efficacy and immune modulatory effects in preclinical models. In a phase I study, KA2507 showed selective target engagement, no significant toxicities, and prolonged disease stabilization in a subset of patients. Further clinical studies of KA2507 are warranted, as a single agent or, preferably, combined with other immuno-oncology drugs.
ALK Inhibitors in Neuroblastoma: A Sprint from Bench to Bedside
Authors: Schulte Johannes H. , Eggert Angelika
Published: May 2021

Activating mutations of the anaplastic lymphoma kinase (ALK) gene were identified in the pediatric tumor neuroblastoma, in 2008. Rapid translation of this finding into targeted neuroblastoma therapy was facilitated by the availability of ALK inhibitors developed for adult malignancies and an efficient preclinical and clinical research program.

See related article by Foster et al., p. 3543
Associations of Stylet Use during Neonatal Intubation with Intubation Success, Adverse Events, and Severe Desaturation: A Report from NEAR4NEOS
Authors: Gray Megan M. , Rumpel Jennifer A. , Brei Brianna K. , Krick Jeanne Alexandra , Sawyer Taylor , Glass Kristen , DeMeo Stephen , Barry James , Ades Anne , Napolitano Natalie , Johnston Lindsay , Moussa Ahmed , Jung Phillip , Quek Bin Huey , Mehrem Ayman Abou , Zenge Jeanne , Shults Justine , Nadkarni Vinay , Kim Jae , Singh Neetu , Tisnic Alicia , Foglia Elizabeth , Nishisaki Akira ,   National Emergency Airway Registry for Neonates: NEAR4NEOS Investigators
Published: May 2021

Introduction: Intubations are frequently performed procedures in neonatal intensive care units (NICU) and delivery rooms (DR). Unsuccessful first attempts are common as are tracheal intubation-associated events (TIAEs) and severe desaturations. Stylets are often used during intubation, but their association with intubation outcomes is unclear. Objective: To compare intubation success, rate of relevant TIAEs, and severe desaturations in neonates intubated with and without stylets. Methods: Tracheal intubations of neonates in the NICU or DR from 16 centers between October 2014 and December 2018, performed by neonatology or pediatric providers, were collected from the NEAR4NEOs international registry. Primary oral intubations with a laryngoscope were included in the analysis. First-attempt success, the occurrence of relevant TIAEs, and severe oxygen desaturation (≥20% saturation drop from baseline) were compared between intubations performed with versus without a stylet. Logistic regression with generalized estimate equations was used to control for covariates and clustering by sites. Results: Out of 5,292 primary oral intubations, 3,877 (73%) utilized stylets. Stylet use varied considerably across the centers with a range between 0.5 and 100%. Stylet use was not associated with first-attempt intubation success, esophageal intubation, mainstem intubation, or severe desaturations after controlling for confounders. Patient size was associated with these outcomes and much more predictive of success. Conclusions: Stylet use during neonatal intubation was not associated with higher first-attempt intubation success, fewer relevant TIAEs, or less severe desaturations. These data suggest that stylets can be used based on individual preference, but stylet use may not be associated with better intubation outcomes.
Evaluation of the Quality of Perinatal Trials: Making the GRADE
Authors: Walsh Verena , McGuire William , Halliday Henry L
Published: May 2021

Background: Assessing the quality of clinical research is a key evidence-based practice skill. Clinicians, guideline producers, policy makers, service commissioners, and families need to have a sense of the validity, applicability, and certainty of research evidence when determining how it should inform their decision-making and practice. Methods: We consider the various methodological and study design factors that contribute to the validity and applicability of clinical research findings. We describe the “Grading of Recommendations Assessment, Development and Evaluation” (GRADE) methodology and discuss how this approach is used to assess and report certainty of evidence and strength of recommendations. Results: The randomized controlled trial (RCT) is the gold standard method for assessing interventions because randomization balances prognostic characteristics between comparison groups. The GRADE approach considers evidence from RCTs as high quality, but acknowledges that the quality and level of certainty of trial evidence may be “downgraded” based on consideration of threats across 5 domains: risk of bias in included trials, inconsistency between trials in outcome estimates, indirectness of the evidence, imprecision of estimates, and likelihood of publication bias. Conclusions: Structured critical appraisal using GRADE methods to assess risk of bias and other threats to the internal and external validity of RCTs and systematic reviews and meta-analyses of their data facilitates transparency and consistency in using evidence to inform policy and practice.
The Quality of life of graduate nursing students in Croatia
Authors: Čivljak Marta , Orešković Stjepan , Milošević Milan , Machala Poplašen Lovela , Sović Slavica , Vukušić-Rukavina Tea
Published: May 2021

Cilj: Cilj provedenog istraživanja bio je ocijeniti kvalitetu života studenata diplomskog
sestrinskog studija pri Medicinskom fakultetu Sveučilišta u Zagrebu
te procijeniti odnos kvalitete života i bračnog statusa, dobne skupine i radnog
okruženja.
Metode: Kvaliteta života studenata sestrinstva anonimno je ispitana korištenjem
upitnika Svjetske zdravstvene organizacije WHOQOL-BREF, kojim su ispitane
četiri domene kvalitete života (domene tjelesnog i psihičkog zdravlja, socijalnih
odnosa i okoline). Provedena je presječna studija u razdoblju od 2012. do
2013. godine među 154 medicinskih sestara i tehničara, studenata diplomskog
studija sestrinstva Medicinskog fakulteta u Zagrebu.
Rezultati: Većina je sudionika (88,3 %) ženskog spola s medijanom od 39 godina
(interkvartni raspon, IQR = 31,1 – 45,2). Više od 90 % sudionika već je prije
završilo neki oblik formalne edukacije na visokoškolskoj razini. Istraživanjem
nije utvrđen značajan utjecaj na ocjenu četiriju domena kvalitete života u odnosu
na bračni status, dobnu skupinu ili radno okruženje. U dobnoj skupini 25 – 45
godina zabilježene su značajno niže vrijednosti medijana (p = 0,010) u psihološkoj
domeni.
Zaključak: Postoji mogućnost da je percepcija kvalitete života bila izravno povezana
s obrazovnim razinama sudionika jer, prema dosadašnjim saznanjima,
medicinske sestre koje su završile edukaciju na visokoškolskoj razini imaju bolju
radnu sposobnost i kvalitetu života te drugačiji pristup i razmišljanje u domenama
koje ispituju kvalitetu života. Pružanje mogućnosti izobrazbe i napretka u
radnom okruženju može doprinijeti smanjenju stope profesionalnog stresa medicinskih
sestara te povećati njihove radne sposobnosti. Druge domene QoL koje
nisu navedene u ovom radu trebale bi se istražiti
Long Noncoding RNA Fos Downstream Transcript Is Developmentally Dispensable but Vital for Shaping the Poststroke Functional Outcome
Authors: Mehta Suresh L. , Chokkalla Anil K. , Kim TaeHee , Bathula Saivenkateshkomal , Chelluboina Bharath , Morris-Blanco Kahlilia C. , Holmes Aleah , Banerjee Anik , Chauhan Anjali , Lee Juneyoung , Venna Venugopal R. , McCullough Louise D. , Vemuganti Raghu
Published: May 2021

Background and Purpose:

Stroke induces the expression of several long noncoding RNAs in the brain. However, their functional significance in poststroke outcome is poorly understood. We recently observed that a brain-specific long noncoding RNA called Fos downstream transcript (FosDT) is induced rapidly in the rodent brain following focal ischemia. Using FosDT knockout rats, we presently evaluated the role of FosDT in poststroke brain damage.

Methods:

FosDT knockout rats were generated using CRISPR-Cas9 genome editing on a Sprague-Dawley background. Male and female FosDT
−/−
and FosDT
+/+
cohorts were subjected to transient middle cerebral artery occlusion. Postischemic sensorimotor deficits were evaluated between days 1 and 7 and lesion volume on day 7 of reperfusion. The developmental expression profile of FosDT was determined with real-time polymerase chain reaction and mechanistic implications of FosDT in the ischemic brain were conducted with RNA-sequencing analysis and immunostaining of pathological markers.

Results:

FosDT expression is developmentally regulated, with the adult cerebral cortex showing significantly higher FosDT expression than neonates. FosDT
−/−
rats did not show any anomalies in growth and development, fertility, brain cytoarchitecture, and cerebral vasculature. However, when subjected to transient focal ischemia, FosDT
−/−
rats of both sexes showed enhanced sensorimotor recovery and reduced brain damage. RNA-sequencing analysis showed that improved poststroke functional outcome in FosDT
−/−
rats is partially associated with curtailed induction of inflammatory genes, reduced apoptosis, mitochondrial dysfunction, and oxidative stress.

Conclusions:

Our study shows that FosDT is developmentally dispensable, mechanistically important, and a functionally promising target to reduce ischemic brain damage and facilitate neurological recovery.
Dār al-Ṭalīʿah and the Question of Arab Authenticity in the 1960s
Authors: Agbaria Ahmad
Published: May 2021

Cultural institutions and publishing houses have been essential to the making of Arab intellectual conversations in the post-colonial era. The publishing house of Dār al-Ṭalīʿah (est. 1959) played a central role in naturalizing social classifications, ideological views and cultural expectations that have influenced the then-new articulation of the notion of Arab authenticity. Yet, al-Ṭalīʿah was more than a publishing house: it was an intellectual hub that sustained intellectuals and unified them into a coherent group. Despite its centrality, however, the group of authors published by al-Ṭalīʿah has rarely drawn the attention of literary critics or intellectual historians. This article rethinks the connection between ideas and their institutional location, rejecting the conventional view that institutions are only secondary to, or even parasitic on, the supremacy of ideas. Looking at the idea of cultural authenticity (aṣālah) fiercely opposed by al-Ṭalīʿah authors, this article examines the ways the publishing house informed the meaning and deployment of aṣālah during the 1960s, even while rejecting it.
Consumer Protection in Jordanian Discount Sales: A Comparative Study with the Legislations of France, Tunisia and the United Arab Emirates
Authors: Kameel Tariq , Alnusair Fayez , Alhajaya Nour
Published: May 2021

This article compares consumer protection in the framework of discounts with the constituent elements of such sales and the relevant methods of protecting consumer rights, according to French, Emirati, Jordanian, and Tunisian legislation and judicial practice. The findings shed light on the operation of consumer rights and market protection, and argues that each legal system has developed divergent means to attain the same goal. While some legal systems have organised sales with detailed rules, others have engaged in very limited market intervention; in the latter case, consumers are prevented from enjoying an important set of rights, as consumer rights and market protection are determined by the merchants.
A new genus and species of Euphaeidae (Odonata, Zygoptera) from the early Eocene Okanagan Highlands locality at Republic, Washington, U.S.A.
Authors: ARCHIBALD S. BRUCE , CANNINGS ROBERT A.
Published: May 2021

We describe Republica weatbrooki, a new genus and species of damselfly (Odonata, Zygoptera, Euphaeidae, Eodichromatinae) from the early Eocene (Ypresian) fossil locality at Republic, Washington, U.S.A. Its single specimen is the sole damselfly known from the Okanagan Highlands series of localities in far-western North America.