bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulating international clinical research: an ethical framework for policy-makers
Authors: Aguilera Bernardo , DeGrazia David , Rid Annette
Published: May 2020

The global distribution of clinical trials is shifting to low-income and middle-income countries (LMICs), and adequate regulations are essential for protecting the rights and interests of research participants in these countries. However, policy-makers in LMICs can face an ethical trade-off: stringent regulatory protections for participants can lead researchers or sponsors to conduct their research elsewhere, potentially depriving the local population of the opportunity to benefit from international clinical research. In this paper, we propose a three-step ethical framework that helps policy-makers to navigate this trade-off. We use a recent set of regulatory protections in Chile to illustrate the practical value of our proposed framework, providing original ethical analysis and previously unpublished data from Chile obtained through freedom of information requests.
Dual but not single PD-1 or TIM-3 blockade enhances oncolytic virotherapy in refractory lung cancer
Authors: Sun Fan , Guo Zong Sheng , Gregory Alyssa D , Shapiro Steven D , Xiao Gutian , Qu Zhaoxia
Published: May 2020

Background

Programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade therapy fails in the majority of patients with cancer. Oncolytic viruses represent a new class of therapeutic agents, yet the therapeutic efficacy is still disappointing. Moreover, intratumoral injection of viruses is the main approach and preclinical studies mainly employ syngeneic or xenograft models.

Methods

Use an endogenous mouse lung cancer model that faithfully recapitulates human lung cancer, and various in vivo, ex vivo and in vitro assays, to investigate the efficacy, mechanism of action and resistance of systemically administered oncolytic vaccinia virus (oVV), immunotherapy and their combination, to find an effective therapy for refractory lung cancer.

Results

Resembling human lung cancers, the majority of which are largely resistant to PD-1/PD-L1 blockade and with decreased PD-L1 expression and T-cell activation by our analysis, urethane-induced endogenous lung tumors in mice show reduced PD-L1 expression, low tumor-infiltrating lymphocytes and innate resistance to PD-1/PD-L1 blockade. Intravenous administration of oVV has efficacy and synergizes with simultaneous but not single blockade of PD-1 and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) in this cancer model. Besides direct tumor cell killing, oVV induces T-cell lung recruitment, tumor infiltration, along with expression of PD-1 and TIM-3 on T cells and PD-1 and TIM-3 ligands on tumor cells and tumor-associated immune cells. Blockade of PD-1 or TIM-3 also causes their mutual induction on T cells.

Conclusions

While systemic administration of oVV shows efficacy in lung cancer by killing tumor cells directly and recruiting and activating T cells for indirect tumor killing, its induction of PD-1 and TIM-3 on T cells and PD-1 and TIM-3 ligands on tumors and tumor-associated immune cells as well as mutual induction of PD-1 or TIM-3 on T cells by their blockade restricts the efficacy of oVV or its combination with single PD-1 or TIM-3 blockade. The triple combination therapy is more effective for refractory lung cancer, and possibly other cold cancers as well.
Resilience in action: leading for resilience in response to COVID-19
Authors: Barton Michelle A , Christianson Marlys , Myers Christopher G , Sutcliffe Kathleen
Published: May 2020

Resilience matters now more than ever in healthcare, with the COVID-19 pandemic putting healthcare providers and systems under unprecedented strain. In popular culture and everyday conversation, resilience is often framed as an individual character trait where some people are better able to cope with and bounce back from adversity than others. Research in the management literature highlights that resilience is more complicated than that – it’s not just something youhave, it’s something youdo. Drawing on research on managing unexpected events, coordinating under challenging conditions, and learning in teams, we distill some counter-intuitive findings about resilience into actionable lessons for healthcare leaders.
AAC Network hard red winter wheat
Authors: Graf R.J. , Larsen R.J. , Beres B.L. , Aboukhaddour R. , Laroche A. , Randhawa H.S. , Foroud N.A.
Published: May 2020

AAC Network is a semi-dwarf hard red winter wheat (Triticum aestivum L.) cultivar that is well adapted across western Canada and eligible for grades of Canada Western Red Winter (CWRW) wheat. It was developed using wheat × maize pollen doubled haploid methodology. AAC Network was evaluated in the Western Canadian Winter Wheat Cooperative registration trials relative to CDC Buteo, Emerson, Moats, and AAC Elevate for 4 yr (2016–2019). Based on 44 replicated trials, AAC Network produced grain yield similar to AAC Elevate, the highest yielding check, with a protein concentration 0.9 units higher. AAC Network had fair to good winter survival, relatively late maturity, short straw with excellent lodging resistance, and high test weight. AAC Network expressed resistance to stem and stripe rust, moderate resistance to leaf rust and common bunt, and intermediate resistance to Fusarium head blight. In addition to increased grain protein concentration, AAC Network showed improvements in gluten strength and flour water absorption, and it maintained the excellent milling yield and low flour ash attributes of the CWRW wheat class.
An infinite square-well potential as a limiting case of a square-well potential in a minimal-length scenario
Authors: Gonçalves A. Oakes O. , Gusson M. F. , Dilem B. B. , Furtado R. G. , Francisco R. O. , Fabris J. C. , Nogueira J. A.
Published: May 2020

One of the most widely problem studied in quantum mechanics is of an infinite square-well potential. In a minimal-length scenario its study requires additional care because the boundary conditions at the walls of the well are not well fixed. In order to avoid this we solve the finite square-well potential whose the boundary conditions are well fixed, even in a minimal-length scenario, and then we take the limit of the potential going to infinity to find the eigenfunctions and the energy equation for the infinite square-well potential. Although the first correction for the energy eigenvalues is the same as one found in the literature, our result shows that the eigenfunctions have the first derivative continuous at the square-well walls what is in disagreement with those previous work. That is because in the literature the authors have neglected the hyperbolic solutions and have assumed the discontinuity of the first derivative of the eigenfunctions at the walls of the infinite square-well which is not correct. As we show, the continuity of the first derivative of the eigenfunctions at the square-well walls guarantees the continuity of the probability current density and the unitarity of the time evolution operator.
Semi-classical approximations based on Bohmian mechanics
Authors: Struyve Ward
Published: May 2020

Semi-classical theories are approximations to quantum theory that treat some degrees of freedom classically and others quantum mechanically. In the usual approach, the quantum degrees of freedom are described by a wave function which evolves according to some Schrödinger equation with a Hamiltonian that depends on the classical degrees of freedom. The classical degrees of freedom satisfy classical equations that depend on the expectation values of quantum operators. In this paper, we study an alternative approach based on Bohmian mechanics. In Bohmian mechanics the quantum system is not only described by the wave function, but also with additional variables such as particle positions or fields. By letting the classical equations of motion depend on these variables, rather than the quantum expectation values, a semi-classical approximation is obtained that is closer to the exact quantum results than the usual approach. We discuss the Bohmian semi-classical approximation in various contexts, such as nonrelativistic quantum mechanics, quantum electrodynamics and quantum gravity. The main motivation comes from quantum gravity. The quest for a quantum theory for gravity is still going on. Therefore a semi-classical approach where gravity is treated classically may be an approximation that already captures some quantum gravitational aspects. The Bohmian semi-classical theories will be derived from the full Bohmian theories. In the case there are gauge symmetries, like in quantum electrodynamics or quantum gravity, special care is required. In order to derive a consistent semi-classical theory it will be necessary to isolate gauge-independent dependent degrees of freedom from gauge degrees of freedom and consider the approximation where some of the former are considered classical.
Triply-charmed hexaquark states with the QCD sum rules
Authors: Wang Zhi-Gang
Published: May 2020

In this paper, we construct the charmed-diquark–charmed-diquark–charmed-diquark-type current to study the axial vector triply-charmed hexaquark state with the QCD sum rules in details. In calculations, we take the energy scale formula [Formula: see text] to choose the pertinent energy scale of the QCD spectral density so as to enhance the pole contribution and improve the convergent behavior of the operator product expansion. If the spin-breaking effects are small for the triply-charmed hexaquark states, the ground state hexaquark states with [Formula: see text], [Formula: see text] and [Formula: see text] are estimated to have the masses about 5.8 GeV and narrow widths.
MORPHOLOGICAL, STRUCTURAL AND OPTICAL CHARACTERIZATIONS OF Zn-DOPED CdS BUFFER LAYER ELABORATED BY CHEMICAL BATH DEPOSITION
Authors: CHERIET H. , MOUALKIA H. , BARILLE R. , ZAABAT M. , MAHROUA O. , TRARI M.
Published: May 2020

Zn-doped CdS layers, with various percentage ratios [Formula: see text] (= [Zn[Formula: see text]]/[Cd[Formula: see text]]%) were grown on glass substrates by chemical bath deposition (CBD). The effect of Zn-doping on different properties of CdS is studied by X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy, atomic force microscopy, energy dispersive X-ray analysis and UV-visible diffuse reflectance. The XRD patterns indicated polycrystalline films with (111) orientation and the insertion of Zn does not change the crystallinity of CdS. The Raman spectra show one major peak centered around 300[Formula: see text]cm[Formula: see text] assigned to the first-order longitudinal optic (LO) phonon modes of CdS. The surface morphology visualized by AFM and SEM analysis showed the influence of the Zn-doping on the morphology of the films, the surface roughness is found to decrease from 16.5 to 8.9[Formula: see text]nm with augmenting the ratio [Formula: see text] from 0 to 6%. In regard to the SEM analysis, the increase of [Formula: see text] yielded a lower porosity of the film and voids, and the films become more homogeneous. The EDAX spectra confirmed the existence of Zn in the doped samples. The bandgap decreases from 2.44 to 2.37[Formula: see text]eV, while the transmittance increases from 76 to 86% with augmenting the ratio [Formula: see text].
THE EFFECT OF VARIOUS CELL PHONE RELATED ACTIVITIES ON GAIT KINEMATICS
Authors: Brennan Alexandra C. , Breloff Scott P.
Published: May 2020

Background: With cell phone use and ownership on the rise, daily circumstances often require individuals to divide attentional resources between walking and a cell phone-related task. This division of attention has been found to detrimentally effect task performance, making pedestrian cell phone usage an increasing safety concern. However, most studies have investigated the impact of dual-tasks on situational awareness and few have focused on tasks other than texting. Therefore, this study aimed to investigate the effect of various cell phone-related tasks on lower limb kinematics during walking.

Methods: Fourteen healthy, college-aged subjects completed gait analysis trials in five walking conditions, one single-task walking condition and four dual task conditions: Walk+Converse, Walk+Read (Simple), Walk+Read (Difficult), and Walk+Text. Subjects’ movements were recorded with a motion capture system and peak sagittal plane lower extremity joint angles, gait velocity, and stride length were calculated.

Results: Of the eight kinematic outcome measures analyzed, all but one revealed some significant (p < 0.05) differences between dual-task walking conditions. Gait velocity and stride length both decreased due to the addition of the dual tasking, with the magnitude of the reduction becoming more apparent with the increased difficulty of the cell phone-based task.

Conclusion: This study supports a fundamental change to gait kinematics in response to cell phone use while walking, with the magnitude of impact being directly related to the complexity of the secondary task. The significant changes to gait kinematics in complex dual-task situations could present a threat to balance.
Deep Roots and Splendid Boughs of the Global Plant Virome
Authors: Dolja Valerian V. , Krupovic Mart , Koonin Eugene V.
Published: May 2020

Land plants host a vast and diverse virome that is dominated by RNA viruses, with major additional contributions from reverse-transcribing and single-stranded (ss) DNA viruses. Here, we introduce the recently adopted comprehensive taxonomy of viruses based on phylogenomic analyses, as applied to the plant virome. We further trace the evolutionary ancestry of distinct plant virus lineages to primordial genetic mobile elements. We discuss the growing evidence of the pivotal role of horizontal virus transfer from invertebrates to plants during the terrestrialization of these organisms, which was enabled by the evolution of close ecological associations between these diverse organisms. It is our hope that the emerging big picture of the formation and global architecture of the plant virome will be of broad interest to plant biologists and virologists alike and will stimulate ever deeper inquiry into the fascinating field of virus–plant coevolution.
Lithium Metal Anode – Advanced Characterization, Slides from the Web Seminar by Dr. Y. Shirley Meng
Authors: Meng Ying Shirley
Published: May 2020

This preprint contains the slides from Prof. Y. Shirley Meng's web seminar on May 18th, 2020, as part of the distinguished lecture series of the Electrochemical Society ECS San Fransisco Section.
A brief history of organoids
Authors: Corrò Claudia , Novellasdemunt Laura , Li Vivian S.W.
Published: May 2020

In vitro cell cultures are crucial research tools for modeling human development and diseases. Although the conventional monolayer cell cultures have been widely used in the past, the lack of tissue architecture and complexity of such model fails to inform the true biological processes in vivo. Recent advances in the organoid technology have revolutionized the in vitro culture tools for biomedical research by creating powerful three-dimensional (3D) models to recapitulate the cellular heterogeneity, structure, and functions of the primary tissues. Such organoid technology enables researchers to recreate human organs and diseases in a dish and thus holds great promises for many translational applications such as regenerative medicine, drug discovery, and precision medicine. In this review, we provide an overview of the organoid history and development. We discuss the strengths and limitations of organoids as well as their potential applications in the laboratory and the clinic.
The Novel Compound Heterozygous Mutations of ECEL1 Identified in a Family with Distal Arthrogryposis Type 5D
Authors: Jin Jie-Yuan , Liu Dan-Yu , Jiao Zi-Jun , Dong Yi , Li Jie , Xiang Rong
Published: May 2020

Introduction. Distal arthrogryposis type 5D (DA5D) is an autosomal recessive disease. The clinical symptoms include contractures of the joints of limbs, especially camptodactyly of the hands and/or feet, unilateral ptosis, a round‐shaped face, arched eyebrows, and micrognathia, without ophthalmoplegia. ECEL1 is a DA5D causative gene that encodes a membrane‐bound metalloprotease. ECEL1 plays important roles in the final axonal arborization of motor nerves in limb skeletal muscles and neuromuscular junction formation during prenatal development. Methods. A DA5D family with webbing of the elbows and fingers was recruited. We performed whole‐exome sequencing (WES) and filtered mutations by disease‐causing genes of arthrogryposis multiplex congenita (AMC). Mutational analysis and cosegregation confirmation were then performed. Results. We identified novel compound heterozygous mutations of ECEL1 (NM_004826: c.69C>A, p.C23∗ and c.1810G>A, p.G604R) in the proband. Conclusions. We detected causative mutations in a DA5D family, expanding the spectrum of known ECEL1 mutations and contributing to the clinical diagnosis of DA5D.
The Neuroprotective Effect of Zingiber cassumunar Roxb. Extract on LPS‐Induced Neuronal Cell Loss and Astroglial Activation within the Hippocampus
Authors: Kongsui Ratchaniporn , Sriraksa Napatr , Thongrong Sitthisak
Published: May 2020

The systemic administration of lipopolysaccharide (LPS) has been recognized to induce neuroinflammation which plays a significant role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In this study, we aimed to determine the protective effect of Zingiber cassumunar (Z. cassumunar) or Phlai (in Thai) against LPS‐induced neuronal cell loss and the upregulation of glial fibrillary acidic protein (GFAP) of astrocytes in the hippocampus. Adult male Wistar rats were orally administered with Z. cassumunar extract at various doses (50, 100, and 200 mg/kg body weight) for 14 days before a single injection of LPS (250 μg/kg/i.p.). The results indicated that LPS‐treated animals exhibited neuronal cell loss and the activation of astrocytes and also increased proinflammatory cytokine interleukin‐ (IL‐) 1β in the hippocampus. Pretreatment with Z. cassumunar markedly reduced neuronal cell loss in the hippocampus. In addition, Z. cassumunar extract at a dose of 200 mg/kg BW significantly suppressed the inflammatory response by reducing the expression of GFAP and IL‐1ß in the hippocampus. Therefore, the results suggested that Z. cassumunar extract might be valuable as a neuroprotective agent in neuroinflammation‐induced brain damage. However, further investigations are essential to validate the possible active ingredients and mechanisms of its neuroprotective effect.
Pushing the Envelope in Obstetric Care: A Case Report of Cesarean Delivery in a Parturient with a BMI >100 kg m−2
Authors: Kumaraswami Sangeeta , Futterman Itamar , Pothula Suryanarayana , Rajendran Geetha P. , Kaul Ashutosh
Published: May 2020

An increasing number of women with a body mass index (BMI) ≥ 60 kg m−2, referred to as super-super obesity, are requiring anesthetic care for labor and delivery. Management of these patients presents obstetric, anesthetic, and logistical challenges. We report our experience in the management of cesarean delivery in a parturient with a BMI of 112 kg m−2. Use of epidural anesthesia and performance of a supraumbilical transverse surgical incision with caudal placement of the panniculus resulted in optimal hemodynamic and ventilatory parameters. Effective multidisciplinary planning and communication is key. We present this case to highlight decision-making strategies and elucidate our approach in the management of this complex obstetric case.
The Induced Membrane Technique for the Management of Segmental Tibial Defect or Nonunion: A Systematic Review and Meta‐Analysis
Authors: Hsu Chen-An , Chen Shih-Heng , Chan Soa-Yu , Yu Yi-Hsun
Published: May 2020

Purpose. To identify the predicting factors for union and infection after applying the induced membrane technique (IMT) for segmental tibial defects. Methods. A systematic review was carried out following the PRISMA guidelines. All databases were searched for articles published between January 2000 and February 2018 using the keywords “Masquelet technique” and “induced membrane technique.” Studies in English reporting more than 5 cases with accessible individual patient data were included. A meta‐analysis was performed. Odds ratios (OR) with 95% confidence intervals were calculated. Results. After reviewing, 11/243 studies (115 patients) were finally selected. The mean age of the patients was 43.6 years (range: 18‐84 years), and the mean length of the tibial defect was 5.5 cm (range: 0‐20 cm). The multivariate logistic regression analysis revealed that the risk factors of postoperative infection after IMT were infected nonunion (p = 0.0160) and defect length ≥ 7 cm (p = 0.0291). Patients with postoperative infection after IMT had a lower union rate (p = 0.0003). Additionally, the use of an antibiotic polymethyl methacrylate cement spacer reduced the need for surgical revision (p = 0.0127). Multiple logistic regression indicated no direct association between the union rate and length of the bone defect. Conclusions. IMT is a reliable and reproducible treatment for segmental tibial defects. However, initial infected nonunion and defect length greater than 7 cm are risk factors for post‐IMT infection, and post‐IMT infection was statistically related to nonunion.
The Effect of Lymphoedema Exercises and Foot Elevation on the Quality of Life of Patients with Elephantiasis
Authors: Watu Emirensiana , Supargiyono  , Haryani
Published: May 2020

Filariasis is a chronic infectious disease caused by filarial worms. Swelling in the legs in patients with filariasis can result in a significantly lower quality of life. The recommended treatments for patients who experience swelling or lymphoedema are lymphoedema exercises and foot elevation. This research is a quantitative study with a quasi-experimental design including pre- and posttreatment tests with a control group. This study used a cluster sampling method, which is a nonprobability sampling technique. The samples in this study were 48 respondents divided into two groups: 24 respondents from the Nebe Village comprising the intervention group and 24 respondents from the Bangkoor Village comprising the control group. The intervention group conducted lymphoedema exercises and foot elevation three times a week for 15–20 min for 1 month and measured their quality of life using the LFSQQ questionnaire. Measurements of pitting edema and ankle diameter were also carried out. Paired t-test revealed an improvement in the quality of life between pretest and posttest in the intervention and control groups (p=0.001). The quality of life in the pre-post intervention group improved from 67.42 to 81.58. In addition, the quality of life in the pre-post control group only improved from 62.50 to 72.58. The level of pitting edema decreased from severe (+++) to moderate (++) and from mild (+) to normal (0), and there was no difference in ankle diameter in each group (p=1.000). The quality of life improved before and after the administration of lymphoedema exercises and foot elevation for each group. Pitting edema decreased before and after lymphoedema exercises and foot elevation for each group. There was no decrease in ankle diameter after lymphoedema exercises and foot elevation in the intervention and control groups.
Bioactivity and Molecular Docking Studies of Derivatives from Cinnamic and Benzoic Acids
Authors: Perez-Castillo Yunierkis , Lima Tamires C. , Ferreira Alana R. , Silva Cecília R. , Campos Rosana S. , Neto João B. A. , Magalhães Hemerson I. F. , Cavalcanti Bruno C. , Júnior Hélio V. N. , de Sousa Damião P.
Published: May 2020

Over the last decade, there has been a dramatic increase in the prevalence and gravity of systemic fungal diseases. This study aimed therefore at evaluating the antifungal potential of ester derivatives of benzoic and cinnamic acids from three Candida species. The compounds were prepared via Fischer esterification, and the antifungal assay was performed by the microdilution method in 96‐well microplates for determining the minimal inhibitory concentrations (MICs). The findings of the antifungal tests revealed that the analogue compound methyl ferulate, methyl o‐coumarate, and methyl biphenyl‐3‐carboxylate displayed an interesting antifungal activity against all Candida strains tested, with MIC values of 31.25‐62.5, 62.5‐125, and 62.5 μg/ml, respectively. A preliminary Structure‐Activity Relationship study of benzoic and cinnamic acid derivatives has led to the recognition of some important structural requirements for antifungal activity. The results of molecular docking indicate that the presence of the enoate moiety along with hydroxyl and one methoxy substitution in the phenyl ring has a positive effect on the bioactivity of compound 7 against Candida albicans. These observations further support the hypothesis that the antifungal activity of compound 7 could be due to its binding to multiple targets, specifically to QR, TS, and ST‐PK. Additional experiments are required in the future to test this hypothesis and to propose novel compounds with improved antifungal activity.
Long Noncoding RNA EZR-AS1 Regulates the Proliferation, Migration, and Apoptosis of Human Venous Endothelial Cells via SMYD3
Authors: You Ganhua , Long Xiangshu , Song Fang , Huang Jing , Tian Maobo , Xiao Yan , Deng Shiyan , Wu Qiang
Published: May 2020

Numerous studies have shown that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of human cardiovascular diseases. However, whether lncRNA ezrin antisense RNA 1 (EZR-AS1) is associated with the progression of coronary heart disease (CHD) remains unclear. Accordingly, the aim of the present study was to evaluate the role of lncRNA EZR-AS1 in patients with CHD and in human venous endothelial cells (HUVECs). The findings revealed that lncRNA EZR-AS1 was highly expressed in the peripheral blood of patients with CHD. In vitro experiments showed that the overexpression of EZR-AS1 could enhance proliferation, migration, and apoptosis by upregulating the expression of EZR in HUVECs; downregulation of lncRNA EZR-AS1 resulted in the opposite effect. lncRNA EZR-AS1 was also found to regulate SET and MYND domain‐containing protein 3 (SMYD3), a histone H3 lysine 4‐specific methyltransferase, which subsequently mediated EZR transcription. Collectively, these results demonstrate that lncRNA EZR-AS1 plays an important role in HUVECs function via SMYD3 signaling.
Jiaweishaoyao Decoction Alleviates DSS-Induced Ulcerative Colitis via Inhibiting Inflammation
Authors: Qiao Huixia , Huang Yahui , Chen Xiaoyan , Yang Long , Wang Yue , Xu Rongrong
Published: May 2020

Purpose. Jiaweishaoyao decoction (JWSYD) is a traditional prescription of Chinese medicine that is initially used for the treatment of diarrhea. This study is aimed at investigating the effects of JWSYD on DSS-induced ulcerative colitis (UC). Methods. DSS-induced UC mice and LPS-induced RAW264.7 cells were used as the UC model in vivo and in vitro. UC was assessed by body weight, disease activity index (DAI), colon length, spleen weight, and histopathological score (HE staining). The levels of TNF-α, IL-1β, and IL-6 were analyzed by ELISA and qRT-PCR. The levels of NLRP3 inflammasome- and NF-κB pathway-associated proteins were measured by western blot. Results. JWSYD alleviated DSS-induced UC in respect to body weight, DAI, colon length, spleen weight, and histopathological score. JWSYD reduced the levels of TNF-α, IL-1β, and IL-6 in DSS-induced UC mice and the supernatants of LPS-induced RAW264.7 cells. JWSYD suppressed the protein levels of inflammasome-associated proteins, including NLRP3, ASC1, Procaspase-1, Cleaved caspase-1, and Cleaved IL-1β in DSS-induced UC mice and LPS-induced RAW264.7 cells. In addition, JWSYD suppressed the NF-κB pathway in vitro and in vivo. Conclusion. JWSYD alleviated DSS-induced UC via inhibiting the NLRP3 inflammasome and NF-κB pathway.
Adaptive Filtering Improved Apnea Detection Performance Using Tracheal Sounds in Noisy Environment: A Simulation Study
Authors: Wu Yanan , Liu Jing , He Baolin , Zhang Xiaotong , Yu Lu
Published: May 2020

Objective. Tracheal sounds were used to detect apnea on various occasions. However, ambient noises can contaminate tracheal sounds which result in poor performance of apnea detection. The objective of this paper was to apply the adaptive filtering (AF) algorithm to improve the quality of tracheal sounds and examine the accuracy of the apnea detection algorithm using tracheal sounds after AF. Method. Tracheal sounds were acquired using a primary microphone encased in a plastic bell, and the ambient noises were collected using a reference microphone resting outside the plastic bell in quiet and noisy environments, respectively. Simultaneously, the flow pressure signals and thoracic and abdominal movement were obtained as the standard signals to determine apnea events. Then, the normalized least mean square (NLMS) AF algorithm was applied to the tracheal sounds mixed with noises. Finally, the algorithm of apnea detection was used to the tracheal sounds with AF and the tracheal sounds without AF. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and Cohen’s kappa coefficient of apnea detection were calculated. Results. Forty‐six healthy subjects, aged 18‐35 years and with BMI < 21.4, were included in the study. The apnea detection performance using tracheal sounds was as follows: in the quiet environment, the tracheal sounds without AF detected apnea with 97.2% sensitivity, 99.9% specificity, 99.8% PPV, 99.4% NPV, 99.5% accuracy, and 0.982 kappa coefficient. The tracheal sounds with AF detected apnea with 98.2% sensitivity, 99.9% specificity, 99.4% PPV, 99.6% NPV, 99.6% accuracy, and 0.985 kappa coefficient. While in the noisy environment, the tracheal sounds without AF detected apnea with 81.1% sensitivity, 96.9% specificity, 85.1% PPV, 96% NPV, 94.2% accuracy, and 0.795 kappa coefficient and the tracheal sounds with AF detected apnea with 91.5% sensitivity, 97.4% specificity, 88.4% PPV, 98.2% NPV, 96.4% accuracy, and 0.877 kappa coefficient. Conclusion. The performance of apnea detection using tracheal sounds with the NLMS AF algorithm in the noisy environment proved to be accurate and reliable. The AF technology could be applied to the respiratory monitoring using tracheal sounds.
Intracellular ROS Scavenging and Anti‐Inflammatory Activities of Oroxylum indicum Kurz (L.) Extract in LPS plus IFN‐γ‐Activated RAW264.7 Macrophages
Authors: Dunkhunthod Benjawan , Talabnin Chutima , Murphy Mark , Thumanu Kanjana , Sittisart Patcharawan , Hengpratom Tanaporn , Eumkeb Griangsak
Published: May 2020

Oroxylum indicum (L.) Kurz has been used as plant‐based food and herbal medicine in many Asian countries. The aim of the present study was to examine the antioxidant and anti‐inflammatory activities of O. indicum extract (O. indicum) in RAW264.7 cells activated by LPS plus IFN‐γ. The phytochemical compounds in O. indicum were identified by GC‐MS and LC‐MS/MS. Five flavonoids (luteolin, apigenin, baicalein, oroxylin A, and quercetin) and 27 volatile compounds were found in O. indicum. O. indicum presented antioxidant activities, including reducing ability by FRAP assay and free radical scavenging activity by DPPH assay. Moreover, O. indicum also suppressed LPS plus IFN‐γ‐activated reactive oxygen species generation in RAW264.7 macrophages. It possessed the potent anti‐inflammatory action through suppressing nitric oxide (NO) and IL‐6 secretion, possibly due to its ability to scavenge intracellular ROS. The synchrotron radiation‐based Fourier transform infrared (SR‐FTIR) spectroscopy results showed the alteration of signal intensity and integrated areas relating to lipid and protein of the activated RAW264.7 macrophages compared to unactivated cells. This is the first report of an application of the SR‐FTIR technique to evaluate biomolecular changes in activated RAW264.7 cells. Our results indicate that O. indicum may be used as a potential source of nutraceutical for the development of health food supplement or a novel anti‐inflammatory herbal medicine.
Identification of a Seven‐lncRNA Immune Risk Signature and Construction of a Predictive Nomogram for Lung Adenocarcinoma
Authors: Jin Donghui , Song Yuxuan , Chen Yuan , Zhang Peng
Published: May 2020

Background. The incidence of lung cancer is the highest of all cancers, and it has the highest death rate. Lung adenocarcinoma (LUAD) is a major type of lung cancer. This study is aimed at identifying the prognostic value of immune‐related long noncoding RNAs (lncRNAs) in LUAD. Materials and Methods. Gene expression profiles and the corresponding clinicopathological features of LUAD patients were obtained from The Cancer Genome Atlas (TCGA). The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was performed on the prognostic immune‐related lncRNAs to calculate the risk scores, and a risk signature was constructed. Survival analysis was performed to assess the prognostic value of the risk signature. A nomogram was also constructed based on the clinicopathological features and risk signature. Results. A total of 437 LUAD patients with gene expression data and clinicopathological features were obtained in this study, which was considered the combination set. They were randomly and equally divided into a training set and a validation set. Seven immune‐related lncRNAs (AC092794.1, AL034397.3, AC069023.1, AP000695.1, AC091057.1, HLA‐DQB1‐AS1, and HSPC324) were identified and used to construct a risk signature. The patients were divided into the low‐ and high‐risk groups based on the median risk score of ‐0.04074. Survival analysis suggested that patients in the low‐risk group had a longer overall survival (OS) than those in the high‐risk group (p = 1.478e − 02). A nomogram was built that could predict the 1‐, 3‐, and 5‐year survival rates of LUAD patients (C‐index of the nomogram was 0.755, and the AUCs for the 1‐, 3‐, and 5‐year survivals were 0.826, 0.719, and 0.724, respectively). The validation and combination sets confirmed these results. Conclusion. Our study identified seven novel immune‐related lncRNAs and generated a risk signature, as well as a nomogram, that could predict the prognosis of LUAD patients.
Anti‐inflammatory, Antibacterial, Toxicological Profile, and In Silico Studies of Dimeric Naphthoquinones from Diospyros lotus
Authors: Rauf Abdur , Abu-Izneid Tareq , Rashid Umer , Alhumaydhi Fahad A. , Bawazeer Saud , Khalil Anees Ahmed , Aljohani Abdullah S. M. , Abdallah Emad M. , Al-Tawaha Abdel Rahman , Mabkhot Yahia Naseer , Shariati Mohammad Ali , Plygun Sergey , Uddin Md. Sahab , Ntsefong Godswill Ntsomboh
Published: May 2020

Diospyros lotus, also known as date‐plum, belongs to the Ebenaceae family and is mostly recognized as a rootstock for D. kaki. Similar classes of naphthoquinones in D. lotus are investigated against cancer and inflammation and have antimicrobial, sedative, and analgesic properties. Six chemical constituents (1‐6) were isolated from Diospyros lotus and tested for anti‐inflammatory effects at the dose of 2.5 and 5 mg/kg, i.p., using carrageenan (1%, 0.05 ml)‐induced paw edema. The maximum protection against carrageenan‐induced edema was observed for compounds 1 and 2. Both studied compounds demonstrated significant anti‐inflammatory effect after the 3rd hour of posttreatment. The maximum anti‐inflammatory effect of compound 1 was 85.96%, while that of compound 2 was 81.44%, followed by compounds 5 and 6, which exhibited 80.11% and 82.45% effect, respectively. Similarly, histamine‐induced inflammation was significantly antagonized by 1, 2, 5, and 6 with 87.99%, 82.18 ± 1.8, 80.40 ± 1.59, and 77.44% effects, respectively, at 5 mg/kg after the 2nd hour of posttreatment. The rest of the tested compounds did not show any significant effect as compared to the negative control. Interestingly, no toxicity was observed at higher doses. Moreover, the extracted compounds showed remarkable antibacterial activity against the Gram‐positive bacteria and no effect against the Gram‐negative bacteria. Docking studies on target cyclooxygenases showed that all the compounds established interactions with the key amino acid residues present in the additional pocket of COX‐2. Hence, these compounds may act as selective COX‐2 inhibitors. In conclusion, the findings of the current study suggest that the roots of Diospyros lotus may contain some anti‐inflammatory and antibacterial agents with minimal toxicological effects and accordingly this plant product is recommended for further investigations.
Design on Universal Circuit Breaker via Improved Gray Wolf Optimization Algorithm
Authors: Dai Shuidong , Xia Kewen , Shi Lili , Xie Min
Published: May 2020

Miniaturization design of the universal circuit breaker is very necessary, but it is not enough to consider only the miniaturization in the design but also consider the energy consumption and breaking capacity of the universal circuit breaker. To this end, a comprehensive optimization design method in this paper is proposed and studied. Firstly, based on the analysis of the universal circuit breaker miniaturization model, combines with the universal circuit breaker’s low energy consumption model and high-segmentation model, a comprehensive optimization model for designing universal circuit breakers is constructed. Secondly, for the comprehensive model solution, an improved gray wolf optimization (GWO) algorithm is proposed, that is, a “cloud model” is introduced to balance the local search and global search capabilities to improve the convergence speed; also, a weight strategy is introduced to avoid falling into the local minimum, and simulations of typical test functions show that the improved algorithm is superior to other algorithms. Finally, the improved gray wolf optimization algorithm is applied to the comprehensive optimization design of universal circuit breakers. The experimental results show that the proposed comprehensive design method is feasible and improves the design accuracy and efficiency of the universal circuit breaker.
Relationship between the 10‐Year Risk for Atherosclerotic Cardiovascular Disease and the Dietary Inflammatory Index among Korean Adults Based on the Seventh Korea National Health and Nutrition Examination Survey (KNHANES)
Authors: Lee Ye-Na , Kang Purum
Published: May 2020

Worldwide, atherosclerotic cardiovascular diseases (ASCVD) are the leading cause of death and are considered a major public health concern. Exposure to repeated inflammation may contribute to the development of ASCVD, and diet plays a vital role in inflammation. In this study, we explored the correlation between the dietary inflammatory index (DII) and the 10‐year ASCVD risk in Korean adults. We used multistage, stratified sampling to analyze a representative sample of Korean adults aged 40‐64 years from the 7th Korea National Health and Nutrition Examination Survey data. Logistic regression was carried out to evaluate the association between 10‐year high risk for ASCVD and dietary variables including DII. Participants were separated by quartiles, from Q1 to Q4, according to DII scores. Participants in the Q1 group had the lowest DII scores indicating a more anti‐inflammatory diet. Participants in the Q4 group had the highest DII scores indicating more proinflammatory diets. Estimated risk of ASCVD results was categorized into the low‐risk (less than 7.5% risk) and high‐risk (greater than 7.5% risk) groups. In men, participants in the Q3 group had a risk for ASCVD of 1.20 times higher than the Q1 group participants and participants in the Q4 group had a risk of 1.34 times higher than the participants in the Q1 group. In women, ASCVD risk was not significantly associated with DII scores. These results provide systematically analyzed evidence for dietary interventions in ASCVD prevention efforts, especially in men.
[Retracted] Iron‐Chelating Agent Can Maintain Bone Homeostasis Disrupted by Iron Overload by Upregulating Wnt/Beta‐Catenin Signaling
Authors: Xu Wei , Yu Ronghua , Zhu Xiaodong , Li Zhikun , Jia Jianjun , Li Dachuan , Chen Yu , Zhang Xiangyang
Published: May 2020

Background. The incidence of osteoporotic fractures is increasing. In this study, we explored the activities of Wnt/β‐catenin signaling in bone tissues with iron accumulation. Methods. We established rat bipedal walking models (RBWM), and a portion of our RBWM rats were intraperitoneally injected with ferric ammonium citrate, normal saline, and deferoxamine. Bone mineral density was measured with a small animal in vivo imaging system. The protein levels of ferritin, TRAP‐5B, RANKL, and OPG in serum were measured by the enzyme‐linked immunosorbent assay (ELISA). Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot were used to quantify the RNA and protein expression levels of certain regulators involved in Wnt/β‐catenin signaling in bone tissues. Results. In the present study, we established a rat bipedal walking model containing 32 bipedal rats, which were randomly classified into four groups, termed as NS, FAC, FAC+NS, and FAC+DFO. Those three experimental groups with FAC injection had significantly lower bone mineral density (BMD) than the control group NS (P < 0.05). The disruption of bone homeostasis and downregulation of Wnt/β‐catenin signaling were also observed in the three groups with FAC injection. Moreover, after the injection of deferoxamine, those aberrations in samples with FAC injection seemed repaired as test results returning or getting close to normal ranges. Conclusion. The osteoporosis could be caused by iron overload, which reduced the bone mineral density by disrupting the homeostasis of bone formation and absorption and attenuating the Wnt/β‐catenin signaling in bone tissues. The deferoxamine had the potential to improve the bone health by reducing the accumulation of iron and increasing the bone mass, which might be a promising therapeutic solution for osteoporosis.
Association between Basal Total Testosterone Levels and Prostate Cancer D’Amico Risk Classes
Authors: Tafuri Alessandro , Sebben Marco , Pirozzi Marco , Processali Tania , Shakir Aliasger , Rizzetto Riccardo , Amigoni Nelia , Brunelli Matteo , Baccaglini Willy , Migliorini Filippo , Siracusano Salvatore , Artibani Walter , Porcaro Antonio Benito
Published: May 2020

Objective: To test the hypothesis that basal total testosterone (TT) serum levels are associated with the D’Amico risk classification at diagnosis of prostate cancer (PCA). Materials and Methods: From November 2014 to March 2018, preoperative basal levels of TT and prostate-specific antigen (PSA) were measured in 601 consecutive PCA patients who were not under androgen deprivation therapy or undergoing prior prostate surgery. Patients were classified into low (reference group), intermediate, and high risk classes according to biopsy findings. The association of TT and other clinical factors with risk classes was evaluated using a multivariate multinomial logistic regression model. Results: According to the D’Amico classification, 124 patients (24%) were low risk, 316 (52.6%) were intermediate risk, and 141 (23.4%) were high risk. Median basal TT circulating levels were significantly increased along clinical risk classes. TT along with PSA, percentage of biopsy positive cores, and tumor clinical stage were independently associated with a high risk (OR = 1.002; p = 0.022) but not with an intermediate risk of PCA when compared to the low risk class. In the intermediate-risk group, endogenous TT together with PSA were independently associated with tumor grade groups 2 (OR = 1.003; p = 0.022) and 3 (OR = 1.003; p = 0.043) compared to grade group 1 cancers. Conclusions: Basal TT levels are positively associated with the D’Amico risk classification, but the association is significant for the high-risk group compared to the low-risk group.
Thyroiditis: A Rare Manifestation of Enasidenib-Induced Differentiation Syndrome
Authors: Annamaraju Pavan , Gopishetty Swathi , Goparaju Naga , Beasey Matthew , Kota Vamsi , Guddati Achuta K.
Published: May 2020

Enasidenib is an FDA-approved isocitrate dehydrogenase 2 (IDH2) inhibitor, which is used in the treatment of acute myeloid leukemia (AML). We present a case of AML with an IDH2 mutation treated with a regimen of enasidenib and 5-azacitidine, where thyroiditis was noted to be a part of differentiation syndrome. The patient is a 77-year-old woman with IDH2-mutated AML who had initially been started on 100 mg of enasidenib and then presented with dyspnea and was diagnosed with pleural effusion – a common presentation with enasidenib – but was also noted to have thyroiditis. She was started on steroids, but due to continued hyperbilirubinemia and thyroiditis, her dose of enasidenib was reduced to half, which resulted in clinical improvement. This case demonstrates thyroiditis as one of the rare manifestations in the treatment of AML with enasidenib-induced differentiation syndrome.
Extracorporeal Photopheresis: A Case of Immunotherapy Ahead of Its Time
Authors: Vieyra-Garcia Pablo Augusto , Wolf Peter
Published: May 2020

Extracorporeal photopheresis (ECP) is a cell-based immunotherapy that involves the reinfusion of autologous leukocytes after exposure to psoralen and UVA. The treatment has been used for over 30 years, at first on patients with cutaneous T-cell lymphoma (CTCL) and later for the management of patients with graft-versus-host disease (GvHD), sclerosing disorders, atopic dermatitis, and other diseases that may share the common driving factor of a pathogenic T-cell clone or clones in blood circulation. Patients with clinical improvement mount an antigen-specific immune response that may have tolerance traits in the case of GvHD or anticlonal cytotoxic characteristics in the case of CTCL. The exact mechanisms that dictate one response or the other are not fully understood, but the evidence accumulated so far indicates that multiple events occur simultaneously and consequentially contribute to the end result. These include contact of cells with the outside (plastics and tubing of the ECP apparatus), exposure to psoralen and UVA that activates platelets, monocytes, and other myeloid cells, the release of damage-associated molecular patterns, differentiation of monocytes into dendritic cells, and generation and successive presentation of numerous antigens after the phagocytosis of apoptotic cells. Once reintroduced, the ECP product increases the frequency and activity of regulatory T cells (Tregs), shifts the systemic cytokine balance, and promotes extravasation of immune cells that together shape the effects of this treatment. In this review, we summarize the seminal work and most recent literature of the therapeutic mechanisms and reflect on future avenues of improvements and applications of ECP.
Several Cases of Ocular Dirofilariasis in Bulgaria
Authors: Velev Valeri
Published: May 2020

Objectives: In this study, we describe ocular dirofilariasis in Bulgaria. Materials and Methods: We studied 7 patients with a subconjunctival or periorbital form of Dirofilaria repens infection during 2010–2019. Morphological, serological, and paraclinical diagnostic methods were used. Results: The patients (6 females, 1 male) were aged between 23 and 72 years. In 3 patients, subcutaneous nodules were detected in the area of the upper eyelid, in 1 patient the location was suborbital. In 3 other patients, a subconjunctival location was found. All patients were cured definitively by removal of the larva, without etiologic treatment. Conclusion: The most reliable and easily accessible diagnostic method is morphological analysis by microscopy of histological preparations of the parasite. In dirofilariasis, ocular location is the most common in humans, and it deserves special attention of clinicians.