bluuebunny/crossref_metadata_2025 huggingface dataset:
Third-generation anti-CD19 chimeric antigen receptor T-cells incorporating a TLR2 domain for relapsed or refractory B-cell lymphoma: a phase I clinical trial protocol (ENABLE)
Authors: George Philip , Dasyam Nathaniel , Giunti Giulia , Mester Brigitta , Bauer Evelyn , Andrews Bethany , Perera Travis , Ostapowicz Tess , Frampton Chris , Li Peng , Ritchie David , Bollard Catherine M , Hermans Ian F , Weinkove Robert
Published: February 2020

Introduction

Autologous T-cells transduced to express a chimeric antigen receptor (CAR) directed against CD19 elicit high response rates in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). However, r/r B-NHL remissions are durable in fewer than half of recipients of second-generation CAR T-cells. Third-generation (3G) CARs employ two costimulatory domains, resulting in improved CAR T-cell efficacy in vitro and in animal models in vivo. This investigator-initiated, phase I dose escalation trial, termed ENABLE, will investigate the safety and preliminary efficacy of WZTL-002, comprising autologous T-cells expressing a 3G anti-CD19 CAR incorporating the intracellular signalling domains of CD28 and Toll-like receptor 2 (TLR2) for the treatment of r/r B-NHL.

Methods and analysis

Eligible participants will be adults with r/r B-NHL including diffuse large B-cell lymphoma and its variants, follicular lymphoma, transformed follicular lymphoma and mantle cell lymphoma. Participants must have satisfactory organ function, and lack other curative options. Autologous T-cells will be obtained by leukapheresis. Following WZTL-002 manufacture and product release, participants will receive lymphodepleting chemotherapy comprising intravenous fludarabine and cyclophosphamide. A single dose of WZTL-002 will be administered intravenously 2 days later. Targeted assessments for cytokine release syndrome and immune cell effector-associated neurotoxicity syndrome, graded by the American Society Transplantation and Cellular Therapy criteria, will be made. A modified 3+3 dose escalation scheme is planned starting at 5×104 CAR T-cells/kg with a maximum dose of 1×106 CAR T-cells/kg. The primary outcome of this trial is safety of WZTL-002. Secondary outcomes include feasibility of WZTL-002 manufacture and preliminary measures of efficacy.

Ethics and dissemination

Ethical approval for the study was granted by the New Zealand Health and Disability Ethics Committee (reference 19/STH/69) on 23 June 2019 for Protocol V.1.2. Trial results will be reported in a peer-reviewed journal, and results presented at scientific conferences or meetings.

Trial registration number

NCT04049513
Impact of an education and multilevel social comparison–based intervention bundle on use of routine blood tests in hospitalised patients at an academic tertiary care hospital: a controlled pre-intervention post-intervention study
Authors: Ambasta Anshula , Ma Irene Wai Yan , Woo Stephen , Lonergan Kevin , Mackay Elizabeth , Williamson Tyler
Published: February 2020

Background

Repetitive inpatient laboratory testing contributes to waste in healthcare. We evaluated an intervention bundle combining education and multilevel social comparison feedback to safely reduce repetitive use of inpatient routine laboratory tests.

Methods

This non-randomised controlled pre-intervention post-intervention study was conducted in four adult hospitals from October 2016 to March 2018. In the medical teaching unit (MTU) of the intervention site, learners received education and aggregate social comparison feedback and attending internists received individual comparison feedback on routine laboratory test utilisation. MTUs of the remaining three sites served as control units. Number and cost of routine laboratory tests ordered per patient-day before and after the intervention was compared with the control units, adjusting for patient factors. Safety endpoints included number of critically abnormal laboratory test results, number of stat laboratory test orders, patient length of stay, transfer rate to the ICU, and 30-day readmission and mortality.

Results

A total of 14 000 patients were included. Pre-intervention and post-intervention groups were similar in age, sex, Charlson Comorbidity Index and length of stay. From the pre-intervention period to the post-intervention period, significantly fewer routine laboratory tests were ordered at the intervention MTU (incidence rate ratio=0.89; 95% CI 0.79 to 1.00; p=0.048) with associated costs savings of $C68 877 (p=0.020) as compared with the control sites. The variability in the ordering pattern of internists at the intervention site also decreased post-intervention. No worsening was noted in the safety endpoints between the pre-intervention and post-intervention period at the intervention unit compared with the controls.

Conclusions

Combination of education and multilevel social comparison feedback significantly andsafelyled to cost savings through reduced use of routine laboratory tests in hospitalised patients.
Correlation of plasma exosomal microRNAs with the efficacy of immunotherapy inEGFR/ALKwild-type advanced non-small cell lung cancer
Authors: Peng Xiao-Xiao , Yu Ruoying , Wu Xue , Wu Shu-Yu , Pi Can , Chen Zhi-Hong , Zhang Xu-Chao , Gao Cun-Yi , Shao Yang W , Liu Li , Wu Yi-Long , Zhou Qing
Published: February 2020

Background

Immunotherapy has become an important treatment option for patients with advanced non-small cell lung cancer (NSCLC). At present, none of these existing biomarkers can effectively stratify true responders and there is an urgent need for identifying novel biomarkers. Exosomes derived from the serum of patients with cancer have been proven to be reliable markers for cancer diagnosis. Here, we explored the possibility of using plasma-derived exosomal microRNAs as potential biomarkers for optimal selection of patients with advancedEGFR/ALKnegative NSCLC to immunotherapy.

Methods

From June 2017 to February 2019, 30 patients with advancedEGFR/ALKwild-type (WT) NSCLC who received PD-1/PD-L1 inhibitors were enrolled. The efficacy evaluation was conducted after every three cycles of treatment according to RECIST 1.1. Plasma samples of these patients were collected before the administration of PD-1/PD-L1 inhibitors as baseline, and after every three cycles if the patients achieved partial response (PR) or complete response. Plasma from seven healthy individuals was also collected as normal control. Exosomes were prepared by ultracentrifugation followed by total RNA extraction, and exosome-derived miRNAs were profiled using small RNA next-generation sequencing followed by differential expression analysis.

Results

In order to identify biomarker for better response, all five patients who achieved PR and four patients with progressive disease (PD) at efficacy evaluation were included for differential expression analysis. Based on unsupervised hierarchical clustering, exosomal miRNA expression profile was significantly altered in patients with NSCLC compared with normal controls with a total of 155 differentially expressed exosomal miRNAs. Interestingly, hsa-miR-320d, hsa-miR-320c, and hsa-miR-320b were identified significantly upregulated in the PD groups compared with the PR group at baseline before the treatment. In addition, we identified that hsa-miR-125b-5p, a T-cell suppressor, showed a trend of increased expression in the PD group at baseline and was significantly downregulated in the post-treatment plasma exosomes compared with pre-treatment samples of the PR patients.

Conclusion

Patients with NSCLC represent unique plasma exosomal miRNA profiles. Hsa-miR-320d, hsa-miR-320c, and hsa-miR-320b were identified as potential biomarkers for predicting the efficacy of immunotherapy in advanced NSCLCs. When T-cell suppressor hsa-miR-125b-5p was downregulated during the treatment, the patients may obtain increased T-cell function and respond well to immunotherapy.
Matched pilot study examining cannabis-based dronabinol for acute pain following traumatic injury
Authors: Schneider-Smith Elisabeth , Salottolo Kristin , Swartwood Claire , Melvin Casey , Madayag Robert M , Bar-Or David
Published: February 2020

Background

To determine whether adjunctive dronabinol, a licensed form of delta-9-tetrahydrocannabinol, reduces opioid consumption when used off-label for managing acute pain following traumatic injury.

Methods

This matched cohort study included patients who were admitted with a traumatic injury between 1 March 2017 and 30 October 2017. The hospital pharmacy database was used to identify patients who received dronabinol (cases), and they were matched 1:1 to patients who did not receive dronabinol (controls) using age, cause of injury and hospital length of stay. The primary outcome, change in opioid consumption, was calculated using morphine milligram equivalents (MME). The change in MME was calculated for cases as total MME over 48 hours with adjunctive dronabinol minus 48 hours prior to dronabinol, and for controls as total MME 48–96 hours from admission minus 0–48 hours from admission. Data are presented as mean and SE or median and IQR. Statistical analysis was performed using paired t-tests and McNemar’s tests.

Results

There were 66 patients included: 33 cases and 33 matched controls. Dronabinol was initiated 55 (28–107) hours from admission. Cases and controls were well matched. Cases had a significant reduction in opioid consumption with adjunctive dronabinol (−79 (20) MME, p<0.001), while opioid consumption was unchanged for controls (−9 (20) MME, p=0.63). This resulted in a ninefold greater reduction in opioid consumption for cases versus controls that was statistically different between pairs (p=0.02). Nineteen (58%) cases reported using marijuana; in this subset, opioid consumption was reduced with adjunctive dronabinol (−97 (24) MME, p<0.001) versus a non-significant increase in opioid consumption in matched controls (11 (29) MME, p=0.70); difference between groups, p=0.01.

Conclusions

The results of this study suggest adjunctive dronabinol reduces opioid consumption following traumatic injury. The opioid-sparing effect of dronabinol may be greater in patients who are marijuana users.

Level of evidence

III.
Statistical sensitivity estimates for oscillating electric dipole moment measurements in storage rings
Authors: Pretz J. , Chang S. P. , Hejny V. , Karanth S. , Park S. , Semertzidis Y. , Stephenson E. , Ströher H.
Published: February 2020

In this paper analytical expressions are derived to describe the spin motion of a particle in magnetic and electric fields in the presence of an axion field causing an oscillating electric dipole moment (EDM). These equations are used to estimate statistical sensitivities for axion searches at storage rings. The estimates obtained from the analytic expressions are compared to numerical estimates from simulations in Chang et al. (Phys Rev D 99(8):083002, 2019). A good agreement is found.
Human-centric Data Dissemination in the IoP
Authors: Mordacchini Matteo , Conti Marco , Passarella Andrea , Bruno Raffaele
Published: February 2020

Data management using Device-to-Device (D2D) communications and opportunistic networks (ONs) is one of the main focuses of human-centric pervasive Internet services. In the recently proposed “Internet of People” paradigm, accessing relevant data dynamically generated in the environment nearby is one of the key services. Moreover, personal mobile devices become proxies of their human users while exchanging data in the cyber world and, thus, largely use ONs and D2D communications for exchanging data directly. Recently, researchers have successfully demonstrated the viability of embedding human cognitive schemes in data dissemination algorithms for ONs. In this article, we consider one such scheme based on the recognition heuristic, a human decision-making scheme used to efficiently assess the relevance of data. While initial evidence about its effectiveness is available, the evaluation of its behaviour in large-scale settings is still unsatisfactory. To overcome these limitations, we have developed a novel hybrid modeling methodology that combines an analytical model of data dissemination within small-scale communities of mobile users, with detailed simulations of interactions between different communities. This methodology allows us to evaluate the algorithm in large-scale city- and countrywide scenarios. Results confirm the effectiveness of cognitive data dissemination schemes, even when content popularity is very heterogenous.
Pattern Guided Integrated Scheduling and Routing in Multi-Hop Control Networks
Authors: Ghosh Sumana , Dey Soumyajit , Dasgupta Pallab
Published: February 2020

Executing a set of control loops over a shared multi-hop (wireless) control network (MCN) requires careful co-scheduling of the control tasks and the routing of sensory/actuation messages over the MCN. In this work, we establish pattern guided aperiodic execution of control loops as a resource-aware alternative to traditional fully periodic executions of a set of embedded control loops sharing a computation and the communication infrastructure. We provide a satisfiability modulo theory–based co-design framework that synthesizes loop execution patterns having optimized control cost as the underlying scheduling scheme together with the associated routing solution over the MCN. The routing solution implements the timed movement of the sensory/actuation messages of the control loops, generated according to those loop execution patterns. From the given settling time requirement of the control loops, we compute a control theoretically sound model using matrix inequalities, which gives an upper bound to the number of loop drops within the finite length loop execution pattern. Next, we show how the proposed framework can be useful for evaluating the fault tolerance of a resource-constrained shared MCN subject to communication link failure.
RNA Droplets
Authors: Rhine Kevin , Vidaurre Velinda , Myong Sua
Published: February 2020

Liquid–liquid phase separation is emerging as the universal mechanism by which membraneless cellular granules form. Despite many previous studies on condensation of intrinsically disordered proteins and low complexity domains, we lack understanding about the role of RNA, which is the essential component of all ribonucleoprotein (RNP) granules. RNA, as an anionic polymer, is inherently an excellent platform for achieving multivalency and can accommodate many RNA binding proteins. Recent findings have highlighted the diverse function of RNA in tuning phase-separation propensity up or down, altering viscoelastic properties and thereby driving immiscibility between different condensates. In addition to contributing to the biophysical properties of droplets, RNA is a functionally critical constituent that defines the identity of cellular condensates and controls the temporal and spatial distribution of specific RNP granules. In this review, we summarize what we have learned so far about such roles of RNA in the context of in vitro and in vivo studies.
Creativity and Bipolar Disorder: A Shared Genetic Vulnerability
Authors: Greenwood Tiffany A.
Published: February 2020

Bipolar disorder is a lifelong mood disorder characterized by extreme mood swings between mania and depression. Despite fitness costs associated with increased mortality and significant impairment, bipolar disorder has persisted in the population with a high heritability and a stable prevalence. Creativity and other positive traits have repeatedly been associated with the bipolar spectrum, particularly among unaffected first-degree relatives and those with milder expressions of bipolar traits. This suggests a model in which large doses of risk variants cause illness, but mild to moderate doses confer advantages, which serve to maintain bipolar disorder in the population. Bipolar disorder may thus be better conceptualized as a dimensional trait existing at the extreme of normal population variation in positive temperament, personality, and cognitive traits, aspects of which may reflect a shared vulnerability with creativity. Investigations of this shared vulnerability may provide insight into the genetic mechanisms underlying illness and suggest novel treatments.
Transnational Professionals
Authors: Harrington Brooke , Seabrooke Leonard
Published: February 2020

This review answers recent calls to consider the transformative role of transnational professionals in contemporary globalization. It departs from the dominant perspective, which views professions as constrained by states’ geographical boundaries and by organizations such as nationally based professional associations. Transnational professionals have particular characteristics: they combine high-level abstract knowledge, high mobility across national and organizational settings, social and cultural capital, and distributed agency to shape global practices. Over the past two decades, a vibrant research stream has emerged on these professionals and their boundary-crossing work, raising new questions about agency, territoriality, and power. We examine transnational professionals across a range of occupations and sectors, as well as world regions, extracting the implications for sociological theory and methods. We outline a scholarly agenda highlighting the opportunity structures and likely trajectories for those who locate themselves in transnational professional spaces, suggesting how they can be investigated in future research.
Sex-specific computational models for blood pressure regulation in the rat
Authors: Ahmed Sameed , Layton Anita T.
Published: February 2020

In the past decades, substantial effort has been devoted to the development of computational models of the cardiovascular system. Some of these models simulate blood pressure regulation in humans and include components of the circulatory, renal, and neurohormonal systems. Although such human models are intended to have clinical value in that they can be used to assess the effects and reveal mechanisms of hypertensive therapeutic treatments, rodent models would be more useful in assisting the interpretation of animal experiments. Also, despite well-known sexual dimorphism in blood pressure regulation, almost all published models are gender neutral. Given these observations, the goal of this project is to develop the first computational models of blood pressure regulation for male and female rats. The resulting sex-specific models represent the interplay among cardiovascular function, renal hemodynamics, and kidney function in the rat; they also include the actions of the renal sympathetic nerve activity and the renin-angiotensin-aldosterone system as well as physiological sex differences. We explore mechanisms responsible for blood pressure and renal autoregulation and notable sexual dimorphism. Model simulations suggest that fluid and sodium handling in the kidney of female rats, which differs significantly from males, may contribute to their observed lower salt sensitivity as compared with males. Additionally, model simulations highlight sodium handling in the kidney and renal sympathetic nerve activity sensitivity as key players in the increased resistance of females to angiotensin II-induced hypertension as compared with males.
Urethral dysfunction in a rat model of chemically induced prostatic inflammation: potential involvement of the MRP5 pump
Authors: Alexandre Eduardo C. , Cao Nailong , Mizoguchi Shinsuke , Saito Tetsuichi , Kurobe Masahiro , Gotoh Daisuke , Okorie Meri , Igarashi Taro , Antunes Edson , Yoshimura Naoki
Published: February 2020

Prostate inflammation (PI) is a clinical condition associated with infection and/or inflammation of the prostate. It is a common disease frequently associated to lower urinary tract (LUT) symptoms. The urethra is an understudied structure in the LUT and plays a fundamental role in the urinary cycle. Here, we proposed to evaluate the effect of PI on the urethra tissue. Male Sprague-Dawley rats were used, and PI was induced by formalin injection into the ventral lobes of the prostate. The pelvic urethra at the prostatic level was harvested for histological analysis, contraction (electrical field stimulation and phenylephrine), and relaxation (sodium nitroprusside/MK-571) experiments. Various gene targets [cytochrome c oxidase subunit 2, transforming growth factor-β1, interleukin-1β, hypoxia-inducible factor-1α, α1A-adrenoceptor, inositol 1,4,5-trisphosphate receptor type 1, voltage-gated Ca2+ channel subunit-α1D, neuronal nitric oxide synthase, soluble guanylyl cyclase, phosphodiesterase 5A, protein kinase CGMP-dependent 1, and multidrug resistance-associated protein 5 (MRP5; ATP-binding cassette subfamily C member 5)] were quantified, and cGMP levels were measured. No histological changes were detected, and functional assays revealed decreased contraction and increased relaxation of urethras from the PI group. The addition of MK-571 to functional assays increased urethral relaxation. Genes associated with inflammation were upregulated in urethras from the PI group, such as cytochrome oxidase c subunit 2, transforming growth factor-β1, interleukin-1β, and hypoxia-inducible factor-1α. We also found increased expression of L-type Ca2+ channels and the neuronal nitric oxide synthase enzyme and decreased expression of the MRP5 pump. Finally, cGMP production was enhanced in urethral tissue of PI animals. The results indicate that PI is associated with proinflammatory gene expression in the urethra without histologically evident inflammation and that PI produces a dysfunctional urethra and MRP5 pump downregulation, which results in cGMP accumulation inside the cell. These findings would help to better understand LUT dysfunctions associated with PI and the role of MRP pumps in the control of LUT function.
Vasopressors and Nutrition Therapy: Safe Dose for the Outset of Enteral Nutrition?
Authors: Simões Covello Luís Henrique , Gava-Brandolis Marcella Giovana , Castro Melina Gouveia , Dos Santos Netos Martins Fidelis , Manzanares William , Toledo Diogo Oliveira
Published: February 2020

Background and Aims. Patients with hemodynamic instability need to receive intensive treatment as fluid replacement and vasoactive drugs. In the meantime, it is supposed to initiate nutritional therapy within 24 to 48 hours after admission to the intensive care unit (ICU), as an essential part of patient’s intensive care and better outcomes. However, there are many controversies tangential to the prescription of enteral nutrition (EN) concomitant to the use of vasopressor and its doses. In this way, the present study aimed to identify what the literature presents of evidence to guide the clinical practice concerning the safe dose of vasopressors for the initiation of nutritional therapy in critically ill patients. Methods. This review was carried out in PubMed, ProQuest, Web of Science, and Medline databases. The descriptors were used to perform the search strategy: Critical Care, Intensive Care Units, Vasoconstrictor Agents, and Enteral Nutrition. Inclusion criteria were patients of both genders, over 18 years of age, using vasoactive drugs, with the possibility of receiving EN therapy, and articles written in English, Portuguese, and Spanish. In addition, exclusion criteria were case reports, non-papers, and repeated papers. Results. 10 articles met our inclusion criteria. Conclusion. It was observed that there are many controversies about the supply of EN in critically ill patients using vasopressor, especially about the safe dose, and it was not possible to identify a cutoff value for the beginning therapy. Despite the drug doses, clinical signs are still the most important parameters in the evaluation of EN tolerance.
MIP-T3 Expression Associated with Defects of Ciliogenesis in Airway of COPD Patients
Authors: Wang Wen-Jun , Yang Shi-Fang , Gao Zhi-Rui , Luo Ze-Ru , Liu Yuan-Ling , Gao Xing-Lin
Published: February 2020

Introduction. Some studies have found that cilia were shorter in COPD smokers than in nonsmokers or healthy smokers. However, the structural abnormalities of cilia and the cause of such abnormalities in COPD patients still remain unknown. Tumor necrosis factor alpha receptor 3 interacting protein 1 (MIP-T3) may play an important role in the progress of ciliary protein transporting. Objectives. This study aimed at exploring the dominated structural abnormalities of cilia and the involvement of MIP-T3 in the pathogenesis of cilia of COPD patients. Methods. Patients who accepted pulmonary lobectomy were divided into 3 groups: the chronic obstructive pulmonary disease (COPD) smoker group, the healthy smoker group, and the nonsmoker group, according to smoking history and pulmonary function. The ultrastructure of cilia and the percentage of abnormal cilia were analyzed using a transmission electron microscope. Real-time PCR, immunohistochemical staining, and western blotting in bronchial epithelium were used to determine MIP-T3 mRNA and protein expression. The relationship between the percentage of abnormal cilia and lung function and MIP-T3 protein expression was analyzed. Results. Patients in the COPD smoker group had increased percentage of abnormal cilia comparing to both the healthy smoker group and the nonsmoker group (both P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P value <0.05). Moreover, the percentage of abnormal cilia was negatively correlated with FEV1, FEV1/FVC ratio, and FEV1%pred (all P values <0.05). Moreover, the MIP-T3 protein expression was positively correlated with the percentage of abnormal cilia (P value <0.05). Conclusions. Our results suggested that the abnormal ciliary ultrastructure, which was common in COPD patients, might be due to MIP-T3 downregulation.
Substance P Administered after Myocardial Infarction Upregulates Microphthalmia-Associated Transcription Factor, GATA4, and the Expansion of c-Kit+ Cells
Authors: Jeong Yun-Mi , Cheng Xian Wu , Kim Weon
Published: February 2020

Microphthalmia-associated transcription factor (MITF), a basic helix-loop-helix leucine zipper transcription factor, can govern gene expression by binding to E box elements in the promoter region of its target gene. Although high levels of MITF have been observed in cardiomyocytes and the heart, the role of MITF after myocardial infarction (MI) remains unclear. We investigated the association between substance P (SP)/neurokinin-1 receptor (NK1R) signaling and MITF expression after MI. Male Sprague-Dawley rats (8 weeks) were randomly divided in two groups: ischemia/reperfusion injury (I/R) and SP injection (5 nmol/kg, SP+I/R). At the end of 7 days, the left ventricle (LV; LV7daysI/R, LV7daysSP+I/R) and infarct-related areas (IA; IA7daysI/R, IA7daysSP+I/R) from the hearts were collected. Immunofluorescence staining demonstrated that the LV7daysSP+I/R had a larger population of c-Kit+ GATA4high cells, which markedly upregulated MITF, c-Kit, and GATA4. c-Kit+ cells in the explant-derived cells (EDCs) derived from IA7daysSP+I/R migrated more widely than EDCs IA7daysI/R. Immunofluorescence staining, western blot analysis, and qRT-PCR assay showed that SP-treated c-Kit+ cells exhibited a high expression of c-Kit, GATA4, and MITF. FTY720 (a MITF inhibitor), RP67580 (NK1R inhibitor), or both inhibited the migration and proliferation of c-Kit+ cells increased by SP and blocked the upregulation of c-Kit, GATA4, and MITF. Overall, we suggest that MITF might be a potential regulator in SP-mediated c-Kit+ cell expansion post-MI via c-Kit and GATA4.
System Prediction and Validation of TCM for Chronic Myeloid Leukemia Treatment from the Perspective of Low‐Toxicity Chemotherapy: A Stilbene α‐Viniferin Has a Proapoptotic Effect on K562 Cells via the Mitochondrial Pathway
Authors: Chai Bing-yang , Gong Fu-Kai , Chen Ze-Hui , Li Zhao-Xue , Zhang Bo
Published: February 2020

Objective. In traditional Chinese medicine (TCM), chronic myeloid leukemia (CML) has been attributed to “poisoned bone marrow,” which is viewed as a loss of Qi or blood, a deficiency in Yin or Yang that causes a complex imbalance between cell growth and death. Malignant myeloid progenitor cells display excessive growth that is difficult to control without toxicity. More than 60 herbs in TCM have shown efficacy against CML. However, the key molecules and mechanisms involved in the holistic‐level characterization, as well as the effective target associations, are still unknown. Methods. The present study employed a computational approach with filtering potential compounds via admetSAR, systems biology‐based functional data prediction, and biochemical and molecular biological validation. Results. We generated 118 bioactive compounds from 11 herbs within four dialectical therapy groups that are most commonly used to treat CML and predicted 141 potential targets. The stilbene resveratrol and its derivatives were found to be highly related to these targets. Among them, α‐viniferin was predicted to target Bcl‐2, caspase‐3, 8, and 9, MAPK14, CDK2, HSP90AA1, and others, reflecting CML therapeutic strategies. In vitro, experimental data showed a nonnecrotic growth limitation of K562 cells caused by α‐viniferin, with an IC50 of 13.61 μg·mL−1 at 24 h. Finally, we validated the chemotherapeutic effect of α‐viniferin in association with a mitochondria‐driven apoptotic mechanism and in sequences entailing mitochondrial dysfunction, which had attributed to the expression of the proapoptotic Bcl‐2 protein and executed K562 cell apoptosis. Conclusions. Our work sheds light on the mechanism of the efficacy of the stilbene α‐viniferin in TCM for the prevention of CML. This work also predicts and validates targets in the mitochondrial signaling pathway, providing a novel strategy for CML treatment.
Botanical Origin and Nutritional Values of Bee Bread of Stingless Bee (Heterotrigona itama) from Malaysia
Authors: Mohammad Salma Malihah , Mahmud-Ab-Rashid Nor-Khaizura , Zawawi Norhasnida
Published: February 2020

Bee bread is the bee-collected pollen with the mixture of honey and bee salivary enzymes, stored inside the bee hive. Malaysia has limited information on bee bread collected by the stingless bee Heterotrigona itama. Therefore, this study aims to determine the botanical origin and nutritional values of bee bread from H. itama. Melissopalynological analysis was performed using scanning electron microscopy (SEM) to determine the bee bread’s botanical origin. The proximate analysis, water activity, sugar profile, amino acid profile, vitamin C content, mineral content, and heavy metal content of the bee bread were analyzed. From the results obtained, Bidens pilosa was found in bee bread from all sampling locations. Bee bread contained high protein (21.70–23.33%) and carbohydrate (57.06–58.89%) contents. Glucose was the predominant sugar found (average 11.499 g/100 g). Eight essential amino acids were quantified, and arginine was detected the highest. The major mineral element in the bee bread was potassium (average 6705.9 mg/kg), followed by phosphorus and magnesium. Toxic metals such as lead, mercury, cadmium, and arsenic were detected but within the safe limits permitted in food. The data obtained contribute towards expanding the knowledge on the nutritional information specifically for H. itama bee bread in Malaysia.
An Efficient Solving Method to Vehicle and Passenger Matching Problem for Sharing Autonomous Vehicle System
Authors: Li Ming , Zheng Nan , Wu Xinkai , Li Weihua , Wu Jianhua
Published: February 2020

With the potential of increasing mobility and reducing cost, shared mobility of autonomous vehicles (AVs) is going to gain solid growth in the coming decade. The major issue for the shared use of AVs is how to project serving routes in an efficiently way. From another perspective, this issue could be understood as to segment maximum number of passengers into groups. Therefore, this paper intends to investigate passengers’ similarity instead of directly matching AVs and passengers. The goal is to determine the minimum number of groups and assign each group with an AV. To this end, a cluster-based algorithm is proposed to classify passengers. Numerical experiments with both small-size and large-size demands are performed to present the validity of the proposed algorithm. Results indicate that the cluster-based algorithm could bring benefit to minimizing the number of vehicles and total travel distance. At last, sensitivity analysis of key parameters shows that vehicle capacity will have little impact when the number of seats exceeds four, and time windows could make continuous influence on gathering passengers.
Damaged Flexibility Matrix Method for Damage Detection of Frame Buildings
Authors: Vaca Oyola Luis S. , Jaime Fonseca Mónica R. , Rodríguez Rocha Ramsés
Published: February 2020

This study presents the damaged flexibility matrix method (DFM) to identify and determine the magnitude of damage in structural elements of plane frame buildings. Damage is expressed as the increment in flexibility along the damaged structural element. This method uses a new approach to assemble the flexibility matrix of the structure through an iterative process, and it adjusts the eigenvalues of the damaged flexibility matrices of each system element. The DFM was calibrated using numerical models of plane frames of buildings studied by other authors. The advantage of the DFM, with respect to other flexibility‐based methods, is that DFM minimizes the adverse effect of modal truncation. The DFM demonstrated excellent accuracy with complete modal information, even when it was applied to a more realistic scenario, considering frequencies and modal shapes measured from the recorded accelerations of buildings stories. The DFM also presents a new approach to simulate the effects of noise by perturbing matrices of flexibilities. This approach can be useful for research on realistic damage detection. The combined effects of incomplete modal information and noise were studied in a ten‐story four‐bay building model taken from the literature. The ability of the DFM to assess structural damage was corroborated. Application of the proposed method to a ten‐story four‐bay building model demonstrates its efficiency to identify the flexibility increment in damaged structural elements.
Clinical and Nonclinical Effects on Operative Duration: Evidence from a Database on Thoracic Surgery
Authors: Wang Jin , Cabrera Javier , Tsui Kwok-Leung , Guo Hainan , Bakker Monique , Kostis John B.
Published: February 2020

Background. Due to the high maintenance costs, it is critical to make full use of operating rooms (ORs). Operative duration is an important factor that guides research on surgery scheduling. Clinical effects, for example, surgery type, rationally influences operative duration. In this study, we also investigate whether the planning and scheduling decisions in ORs influence the operative duration. Methods. For our study, we collected and reviewed data on 2,451 thoracic operations from a large hospital in China. The study was conducted over a period of 34 months. Linear and nonlinear regression models were used to detect the effects on the duration of the operations. We have also examined interactions between the factors. Results. Operative duration decreased with the number of operations a surgeon performed in a day (P<0.001). It was also found that operative duration decreased with the number of operations allocated to an OR, as long as there were not more than four surgeries per day (P<0.001). However, they increased with the number of operations if it was more than four (P<0.01). The duration of surgery was affected by its position in the sequencing of surgeries performed by a surgeon. In addition, the effects of surgeons depend on the surgery type as well as the position in the sequencing order. Conclusions. Operative duration was affected not only due to clinical effects but also some nonclinical effects. Scheduling decisions significantly influenced operative duration.
Novel Fluorescent Mitochondria-Targeted Probe MitoCLox Reports Lipid Peroxidation in Response to Oxidative Stress In Vivo
Authors: Lyamzaev Konstantin G. , Panteleeva Alisa A. , Karpukhina Anna A. , Galkin Ivan I. , Popova Ekatherina N. , Pletjushkina Olga Yu. , Rieger Bettina , Busch Karin B. , Mulkidjanian Armen Y. , Chernyak Boris V.
Published: February 2020

A new mitochondria-targeted probe MitoCLox was designed as a starting compound for a series of probes sensitive to cardiolipin (CL) peroxidation. Fluorescence microscopy reported selective accumulation of MitoCLox in mitochondria of diverse living cell cultures and its oxidation under stress conditions, particularly those known to cause a selective cardiolipin oxidation. Ratiometric fluorescence measurements using flow cytometry showed a remarkable dependence of the MitoCLox dynamic range on the oxidation of the sample. Specifically, MitoCLox oxidation was induced by low doses of hydrogen peroxide or organic hydroperoxide. The mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decyltriphenyl-phosphonium (SkQ1), which was shown earlier to selectively protect cardiolipin from oxidation, prevented hydrogen peroxide-induced MitoCLox oxidation in the cells. Concurrent tracing of MitoCLox oxidation and membrane potential changes in response to hydrogen peroxide addition showed that the oxidation of MitoCLox started without a delay and was complete during the first hour, whereas the membrane potential started to decay after 40 minutes of incubation. Hence, MitoCLox could be used for splitting the cell response to oxidative stress into separate steps. Application of MitoCLox revealed heterogeneity of the mitochondrial population; in living endothelial cells, a fraction of small, rounded mitochondria with an increased level of lipid peroxidation were detected near the nucleus. In addition, the MitoCLox staining revealed a specific fraction of cells with an increased level of oxidized lipids also in the culture of human myoblasts. The fraction of such cells increased in high-density cultures. These specific conditions correspond to the initiation of spontaneous myogenesis in vitro, which indicates that oxidation may precede the onset of myogenic differentiation. These data point to a possible participation of oxidized CL in cell signalling and differentiation.
The Association of Stage 1 Hypertension Defined by the 2017 ACC/AHA Guideline with Stroke and Its Subtypes among Elderly Chinese
Authors: Gao Jinyue , Dai Yue , Xie Yanxia , Zheng Jia , Wang Yali , Guo Rongrong , Sun Zhaoqing , Xing Liying , Zhang Xingang , Sun Yingxian , Zheng Liqiang
Published: February 2020

Background. The 2017 American College of Cardiology and American Heart Association hypertension guideline updated stage 1 hypertension definition as systolic blood pressure range from 130 to 139 mmHg or diastolic blood pressure from 80 to 89 mmHg. However, the association of stage 1 hypertension with stroke and its subtypes among the older population in rural China remains unclear. Methods. This population‐based cohort study consisted of 7,503 adults aged ≥60 years with complete data and no cardiovascular disease at baseline from rural areas of Fuxin County, Liaoning province, China. Follow‐up for the new cases of stroke was conducted from the end of the baseline survey to the end of the third follow‐up survey (January 1, 2007–December 31, 2017). Adjusted Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals with the normal blood pressure as a reference, and calculated population attributable risk was based on prevalence and hazard ratios. Results. During a median follow‐up of 12.5 years, we observed 1,159 first‐ever incident stroke (774 ischemic, 360 hemorrhagic, and 25 uncategorized). With the blood pressure <120/<80 mmHg as a reference, stage 1 hypertension showed the adjusted hazard ratios (95% confidence intervals) of 1.45 (1.11–1.90) for all stroke, 1.65 (1.17–2.33) for ischemic stroke, and 1.17 (0.74–1.85) for hemorrhagic stroke, respectively. In this study, the population attributable risk values of stage 1 hypertension were 10.22% (2.64%–18.56%) for all stroke and 14.34% (4.23%–25.41%) for ischemic stroke. Conclusion. Among adults aged ≥60 years in rural China, stage 1 hypertension defined by 2017 American College of Cardiology and American Heart Association hypertension guideline was independently associated with the increased risk of all stroke and ischemic stroke, excluding hemorrhagic stroke.
Cooperative U-Turn Merging Behaviors and Their Impacts on Road Traffic in CVIS Environment
Authors: Wu Wenjing , Sun Renchao , Li Yongxing , Chen Runchao
Published: February 2020

U-turn behavior of vehicle is one of the main causes of urban traffic congestion and accidents. A collaborative U-turn merging control algorithm is studied with collision avoidance and delay minimization for vehicles under Cooperative Vehicle Infrastructure System (CVIS) environment. Two control strategies, zip merging and platoon merging control, are proposed. The applicability of these two strategies is compared from the perspective of efficiency and driving comfort. The cellular automaton simulation system composed of a two-way four-lane traffic flow with a U-turn facility in middle of road is established with cooperative control algorithm imbedded. The influence of cooperative U-turn merging behaviors on traffic performance is evaluated by analyzing the arrival rates of main lane and U-turn vehicles and their relationship between one another. The simulation results show that the arrival rate of vehicles on target lane has a great impact on traffic delay. The cooperative control can improve the traffic flow only in the condition that the arrival rate of vehicles on target lane is less than 0.7. It provides some practical references for transportation agencies to meet efficiency requirements of the U-turn section when they apply cooperative control strategy.
Serum Sclerostin, Body Composition, and Sarcopenia in Hemodialysis Patients with Diabetes
Authors: Medeiros Maria Carolina , Rocha Natalia , Bandeira Elba , Dantas Isabel , Chaves Conceição , Oliveira Mario , Bandeira Francisco
Published: February 2020

Sclerostin (Scl) is an osteoblast-inhibiting glycoprotein that is secreted mainly by osteocytes and is regulated by hormonal changes and skeletal loading. Decreased physical function and high serum Scl concentrations have been reported in chronic renal failure patients but little is known to date about the differences between diabetic and non-diabetic patients on hemodialysis who are susceptible to both sarcopenia and bone fragility. Objective.To determine the prevalence of sarcopenia and its association with serum Scl concentrations and metabolic parameters in 92 patients on hemodialysis. Anthropometric data and physical performance were evaluated in this study. Blood samples were collected for Scl, glucose, cholesterol, triglycerides, calcium, phosphate, PTH, and 25 OH-vitamin D measurements. Lean mass was evaluated using multifrequency electro-bioimpedance after dialysis session. Results. Mean age was 63.3 ± 13.6 years, 63% of patients were male, and 44.6% had diabetes. Mean body mass index (BMI) was higher in diabetics (26.6 ± 5.2 vs. 24.1 ± 3.7; p=0.01) and there were no differences in gait speed and handgrip strength between diabetic and non-diabetic subjects. A low skeletal muscle mass index (SMI) was identified in 65.2% of the participants, and among them 76.7% were men and 36.7% were diabetics. Mean serum Scl was 86.9 ± 39.0 pmol/L, which was higher in men (94.6 ± 41.7; p=0.017), in those individuals with low SMI (94.9 ± 40.7; p<0.001), and in diabetics (97.2 ± 46.6; p<0.003). After multivariate analysis and adjustments for potential confounders, high serum Scl was independently associated with low SMI and with the presence of diabetes. The following variables correlated positively with diabetes: blood pressure; BMI; waist circumference; waist/hip ratio; plasma glucose; serum Scl; and fat mass. Conclusions. We found higher serum Scl concentrations in hemodialysis patients with diabetes and these were inversely related to muscle mass.
Surgical Management of Complications after Dexamethasone Implant
Authors: Sborgia Giancarlo , Niro Alfredo , D’Oria Francesco , Galeone Alessandra , Sborgia Luigi , Boscia Francesco , Sborgia Alessandra , Alessio Giovanni
Published: February 2020

Purpose. To report surgical management of ocular complications occurred after dexamethasone (DEX) implant (Ozurdex®) injection. Methods. Retrospective interventional case series. Results. Different surgical procedures including viscoexpression to manage the migration of the implant into the anterior chamber, “phaco-rolling” technique for the intralenticular injection, and vitrectomy with implant removal for an acute endophthalmitis were performed. Successful management of different complications after DEX implant by using individualized surgical approaches was observed. Conclusions. Early and targeted surgical management is required in selected cases of ocular complications after DEX implant. The implant removal was needed to preserve ocular anatomy and function.
Prevalence of Alcohol Use Disorders and Their Association with Sociodemographic Determinants and Depression/Anxiety Disorders in a Representative Sample of the Greek General Population
Authors: Bellos Stefanos , Petrikis Petros , Malliori Meni , Mavreas Venetsanos , Skapinakis Petros
Published: February 2020

Background. Country-level epidemiological data about alcohol-related problems is useful for planning prevention and treatment services. Heavy Alcohol Consumption (HAC) and Alcohol Use Disorder (AUD) are two syndromes of alcohol-related problems that have been recognized worldwide. Study of the epidemiological determinants of HAC and AUD in different sociocultural contexts could inform hypotheses about the etiology or the consequences of alcohol-related problems. Objectives. We assessed the prevalence and associations of HAC and AUD with sociodemographic variables adjusting for common mental disorders in a representative sample of the general population of Greece (N=4894 participants). The period of data collection just preceded the emergence of the financial crisis in Greece. Results. The majority of the population did not report HAC, AUD or abstinence from alcohol. HAC was reported by 12.7% (95% CI: 11.8–13.6) of the population while 3.1% (95% CI: 2.7–3.6) met criteria for AUD. Younger age, divorce, lower educational level, living in an urban area, physical health problems, and smoking were associated with a higher prevalence of both conditions. Presence of severe financial difficulties and never married family status were associated with a higher prevalence of HAC but not AUD. HAC was associated with nonspecific psychiatric morbidity while AUD was associated with more specific psychiatric disorders. Conclusion/Importance. Both alcohol-related problems are frequent in the general population and have common and distinct determinants. The comparison between the findings of our study and those of similar studies during or after the period of financial austerity in Greece, would offer the opportunity to assess the possible effects of changes in the economical context in the determinants of alcohol-related problems.
Adsorption of Thymol onto Natural Clays of Morocco: Kinetic and Isotherm Studies
Authors: Ziyat Hamid , Naciri Bennani Mohammed , Hajjaj Hassan , Qabaqous Omar , Arhzaf Said , Mekdad Soumiya , Allaoui Safae
Published: February 2020

The present work aims to study the affinity of a component of the thyme essential oil “thymol” to natural Moroccan clay “Rhassoul” using the adsorption technique. The physicochemical characterizations of the purified and modified clay were carried out by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), DTA/TGA, and SEM-EDX. Thymol adsorption tests on the purified Rhassoul (Rh-P) and the modified one by CTAB (Rh-CTAB) were followed by UV-visible spectroscopy. They show that the adsorption isotherms can be described by the Freundlich model and that the kinetics of adsorption is in accordance with the pseudo-second-order model for the two clays. Adsorption capacities obtained were of the order of 6 mg/g for the purified Rhassoul and 16 mg/g for the modified Rhassoul by cetyltrimethylammonium bromide (CTAB). These values show that the modified Rhassoul has a better adsorption capacity compared to the purified Rhassoul.