bluuebunny/crossref_metadata_2025 huggingface dataset:
Out-of-pocket expenses related to aging in place for frail older people: a scoping review protocol
Authors: Moody Elaine , Martin-Misener Ruth , Warner Grace , Macdonald Marilyn , Weeks Lori E. , Shaw Lynn , McKibbon Shelley
Published: March 2019

Objective:

The objective of this scoping review is to describe the available evidence reporting out-of-pocket expenses for aging-in-place for frail older people and their caregivers.

Introduction:

There has been an increased focus on supporting frail older people to live in the community, rather than in costly long-term residential care. The out-of-pocket expenses associated with supporting older people with frailty to remain in their homes and communities contribute to caregiver burden and can influence decisions about where to live.

Inclusion criteria:

This scoping review will consider literature on community-dwelling older people 60 years and older who have been identified as frail. Research and policy papers that report the out-of-pocket expenses incurred by older people with frailty or by their family or friend caregivers to support aging well at home will be included. Studies in English will be considered with no date restriction.

Methods:

The search strategy aims to find both published and unpublished literature (e.g. policy papers, theses and dissertations). Search databases include CINAHL, PubMed, Scopus, Embase, PsycINFO, Sociological Abstracts, and Public Affairs Index, as well as databases of unpublished sources. The language will be limited to English or French. Title and abstract screening, as well as full-text screening, will be completed by two reviewers. Data will be charted to describe the body of literature focusing on elements such as type of literature, methods used, setting and out-of-pocket expenses. Data will be presented graphically when possible, and accompanied by a narrative that describes the characteristics of the body of literature.
Prey preference, reproductive performance, and life table of Amblyseius tsugawai (Acari: Phytoseiidae) feeding on Tetranychus urticae and Bemisia tabaci
Authors: Yang Jingyi , Lv Jiale , Liu Jingyue , Xu Xuenong , Wang Endong
Published: March 2019

Amblyseius tsugawai is a phytoseiid species distributed in Asia. In the present study, laboratory experiments were conducted to investigate its preference to prey stages when feeding on Tetranychus urticae and Bemisia tabaci, to evaluate its development and reproduction, and to estimate its life table parameters on each of the two prey species. Our results indicate that A. tsugawai shows preference to larvae of T. urticae, and to eggs of B. tabaci. When the two preferred stages were provided together, A. tsugawai randomly selected its prey. No significant difference in developmental times of A. tsugawai was observed when reared on T. urticae (6.75 days) and B. tabaci (7.05 days). In contrast, cumulative fecundity of A. tsugawai was only 14.6% when reared on B. tabaci (4.6 eggs/female) than on T. urticae (31.5 eggs/female). Impact of prey for both females and males on reproduction were also observed. Comparing to the treatment when both parents were reared on T. urticae, A. tsugawai fecundity was reduced by ca. 48.2% when the male was reared on B. tabaci, and was reduced by 86.5% and 88.8% when the female or both parents were reared on B. tabaci, respectively. Amblyseius tsugawai is the first indigenous phytoseiid species of China to show a positive intrinsic rate of population increase (0.013) when reared on B. tabaci as the only prey. The potential of A. tsugawai in greenhouse whitefly control is discussed.
Microspalax atlanticus sp. nov. (Acariformes: Alloptidae), the first feather mite from a procellariiform bird in Brazil (Aves: Procellariiformes)
Authors: Hernandes Fabio Akashi
Published: March 2019

A new feather mite species of the genus Microspalax Mégnin & Trouessart, 1884 (Alloptidae: Microspalacinae) is described from the Atlantic petrel, Pterodroma incerta (Schlegel, 1863), in Brazil. Males of M. atlanticus sp. nov. differ from M. pterodromae Dubinin, 1949 mostly by the wider opisthogastric shields and setae ps3 inserted at posterior third of that shield. This is the first representative of the genus described from Brazil, and the first feather mite described from a procellariiform bird in the country. A key to males of Microspalax species is presented.
Parasitism of mosquitoes (Diptera: Culicidae) by water mite larvae (Acari: Hydrachnidia) in Amol, Mazandaran Province, northern Iran
Authors: Karami Mohsen , Saboori Alireza , Asadi Mahdieh , Moosa-Kazemi Seyed Hassan , Gorouhi Mohammad Amin , Motevali Haghi Farzad , Maleki-Ravasan Naseh , Zagedi Golpayegani Azadeh
Published: March 2019

Mosquitoes transmit a wide range of vector-borne diseases to humans and animal. Due to the increase in insecticide resistance, there is a need for novel mosquito vector control programs, including biocontrol. Some water mite larvae, such as those of Arrenurus genus, act as parasites of mosquitoes. Mosquito larvae, pupae and adults were collected from three locations in Amol County, Iran by dipping and hand-catch collection methods, from May to late September 2015. Then mites were removed from mosquitoes and identified to genus level using valid identification keys. A total of 873 adults of anopheline mosquitoes belonging to three species (Anopheles maculipennis s.lat., An. pseudopictus and An. hyrcanus) were collected. We only found Arrenurus sp. mites. From 873 anopheline mosquitoes captured, 11% were parasitized by 151 mites, with a mean rate of 1.59, ranging from 1 to 14. Parasitism was higher in lowlands. Water mites, as biocontrol agents of vectors, could impact fecundity, fertility and induce other harms on host. As this study is the first research on water mite parasitism on mosquitoes in Iran, more detailed studies are needed to increase our knowledge on biology and ecology of water mites parasitizing mosquitoes in Amol and other areas in Caspian sea region in Iran.
Measuring the magnetization of a permanent magnet
Authors: Barman B. , Petrou A.
Published: March 2019

The effect of an external magnetic field B on magnetic materials is a subject of immense importance. The simplest and oldest manifestation of such effects is the behavior of the magnetic compass. Magnetization M plays a key role in studying the response of magnetic materials to B. In this paper, an experimental technique for the determination of M of a permanent magnet will be presented. The proposed method discusses the effect of B (produced by a pair of Helmholtz coils) on a permanent magnet, suspended by two strings and allowed to oscillate under the influence of the torque that the magnetic field exerts on the magnet. The arrangement used Newton's second law for rotational motion to measure M via graphical analysis.
Multiplexed CRISPR-Cas9-Based Genome Editing of
Rhodosporidium toruloides
Authors: Otoupal Peter B. , Ito Masakazu , Arkin Adam P. , Magnuson Jon K. , Gladden John M. , Skerker Jeffrey M.
Published: March 2019

Microbial biofuel and bioproduct platforms provide access to clean and renewable carbon sources that are more sustainable and environmentally friendly than petroleum-based carbon sources. Furthermore, they can serve as useful conduits for the synthesis of advanced molecules that are difficult to produce through strictly chemical means.
R. toruloides
has emerged as a promising potential host for converting renewable lignocellulosic material into valuable fuels and chemicals. However, engineering efforts to improve the yeast’s production capabilities have been impeded by a lack of advanced tools for genome engineering. While this is rapidly changing, one key tool remains unexplored in
R. toruloides
: CRISPR-Cas9. The results outlined here demonstrate for the first time how effective multiplexed CRISPR-Cas9 gene disruption provides a framework for other researchers to utilize this revolutionary genome-editing tool effectively in
R. toruloides
.
Proximity Staining Using Enzymatic Protein Tagging in Diplomonads
Authors: Ástvaldsson Ásgeir , Hultenby Kjell , Svärd Staffan G. , Jerlström-Hultqvist Jon
Published: March 2019

The function of many proteins is intrinsically related to their cellular location. Novel methods for ascertainment of the ultrastructural location of proteins have been introduced in recent years, but their implementation in protists has so far not been readily realized. Here, we present an optimized proximity labeling protocol using the APEX system in the salmon pathogen
Spironucleus salmonicida
. This protocol was also applicable to the human pathogen
Giardia intestinalis
. Both organisms required extraneous addition of hemin to the growth medium to enable detectable peroxidase activity. Further, we saw no inherent limitation in labeling efficiency coupled to the cellular compartment, as evident with some other proximity labeling systems. We anticipate that the APEX proximity labeling system might offer a great resource to establish the ultrastructural localization of proteins across genetically tractable protists but might require organism-specific labeling conditions.
Navigation-guided biopsy of retropharyngeal lymph nodes
Authors: Hallak Bassel , Von Wihl Sonia , Boselie Franciscus , Bouayed Salim
Published: March 2019

The impact of metastasis to the retropharyngeal lymph node group is poorly understood because of the difficult access to the retropharyngeal space (RPS). In 20%–50% of surgically treated oropharyngeal, hypopharyngeal, and cervical oesophageal carcinomas, we can find metastases to the retropharyngeal lymph nodes (RPLNs).
1
The use of a three-dimensional (3D)-imaging-guided navigation system to perform a biopsy for a suspicion of metastasis in an RPLN can provide advantages in terms of better precision and 3D orientation with protection of the surrounding critical structures. We report two cases of an open biopsy by transoral and transnasal approaches for a suspicion of metastasis in a retropharyngeal lymph node in two patients with oropharyngeal and pulmonary cancer, respectively, by using the 3D imaging-guided navigation system. In the both cases, the biopsies performed were very accurate and allowed to get a full histological analysis and diagnosis. The use of the navigation system as a means to perform biopsies in the soft tissue of the neck is rarely reported and up to date few reports can be found in the literature. This technique can provide multiple advantages when compared with other conventional methods. The procedure is simple, safe and minimally invasive.
Are perceived barriers to accessing mental healthcare associated with socioeconomic position among individuals with symptoms of depression? Questionnaire-results from the Lolland-Falster Health Study, a rural Danish population study
Authors: Packness Aake , Halling Anders , Simonsen Erik , Waldorff Frans Boch , Hastrup Lene Halling
Published: March 2019

Objective

To evaluate if perceived barriers to accessing mental healthcare (MHC) among individuals with symptoms of depression are associated with their socio-economic position (SEP).

Design

Cross-sectional questionnaire-based population survey from the Lolland-Falster Health Study (LOFUS) 2016–17 of 5076 participants.

Participants

The study included 372 individuals, with positive scores for depression according to the Major Depression Inventory (MDI), participating in LOFUS .

Interventions

A set of five questions on perceived barriers to accessing professional care for mental health problem was posed to individuals with symptoms of depression (MDI score >20).

Outcomes

The association between SEP (as measured by educational attainment, employment status and financial strain) and five different types of barriers to accessing MHC were analysed in separate multivariable logistic regression models adjusted for gender and age.

Results

A total of 314 out of 372 (84%) completed the survey questions and reported experiencing barriers to MHC access. Worry about expenses related to seeking or continuing MHC was a considerable barrier for 30% of the individuals responding and, as such, the greatest problem among the five types of barriers. 22% perceived Stigma as a barrier to accessing MHC, but there was no association between perceived Stigma and SEP. Transportation was not only the barrier of least concern for individuals in general but also the issue with the greatest and most consistent socio-economic disparity (OR 2.99, 95% CI 1.19 to 7.52) for the lowest vs highest educational groups and, likewise, concerning Expenses (OR 2.77, 95% CI 1.34 to 5.76) for the same groups.

Conclusion

Issues associated with Expenses and Transport were more frequently perceived as barriers to accessing MHC for people in low SEP compared with people in high SEP. Stigma showed no association with SEP.

Informed written consent was obtained. Region Zealand’s Ethical Committee on Health Research (SJ-421) and the Danish Data Protection Agency (REG-24–2015) approved the study.
Modeling and Computational Characterization of Twitter Customer Service Conversations
Authors: Oraby Shereen , Bhuiyan Mansurul , Gundecha Pritam , Mahmud Jalal , Akkiraju Rama
Published: March 2019

Given the increasing popularity of customer service dialogue on Twitter, analysis of conversation data is essential to understanding trends in customer and agent behavior for the purpose of automating customer service interactions. In this work, we develop a novel taxonomy of fine-grained “dialogue acts” frequently observed in customer service, showcasing acts that are more suited to the domain than the more generic existing taxonomies. Using a sequential SVM-HMM model, we model conversation flow, predicting the dialogue act of a given turn in real time, and showcase this using our “PredDial” portal. We characterize differences between customer and agent behavior in Twitter customer service conversations and investigate the effect of testing our system on different customer service industries. Finally, we use a data-driven approach to predict important conversation outcomes: customer satisfaction, customer frustration, and overall problem resolution. We show that the type and location of certain dialogue acts in a conversation have a significant effect on the probability of desirable and undesirable outcomes and present actionable rules based on our findings. We explore the correlations between different dialogue acts and the outcome of the conversations in detail using an actionable-rule discovery task by leveraging a state-of-the-art sequential rule mining algorithm while modeling a set of conversations as a set of sequences. The patterns and rules we derive can be used as guidelines for outcome-driven automated customer service platforms.
Profiling Personality Traits with Games
Authors: Santos Carlos Pereira , Hutchinson Kevin , Khan Vassilis-Javed , Markopoulos Panos
Published: March 2019

Trying to understand a player's characteristics with regards to a computer game is a major line of research known as player modeling. The purpose of player modeling is typically the adaptation of the game itself. We present two studies that extend player modeling into player profiling by trying to identify abstract personality traits, such as the
need for cognition
and
self-esteem
, through a player's in-game behavior. We present evidence that game mechanics that can be broadly adopted by several game genres, such as hints and a player's self-evaluation at the end of a level, correlate with the aforementioned personality traits. We conclude by presenting future directions for research regarding this topic, discuss the direct applications for the games industry, and explore how games can be developed as profiling tools with applications to other contexts.
A Comparison of Adaptive View Techniques for Exploratory 3D Drone Teleoperation
Authors: Thomason John , Ratsamee Photchara , Orlosky Jason , Kiyokawa Kiyoshi , Mashita Tomohiro , Uranishi Yuki , Takemura Haruo
Published: March 2019

Drone navigation in complex environments poses many problems to teleoperators. Especially in three dimensional (3D) structures such as buildings or tunnels, viewpoints are often limited to the drone’s current camera view, nearby objects can be collision hazards, and frequent occlusion can hinder accurate manipulation.

To address these issues, we have developed a novel interface for teleoperation that provides a user with environment-adaptive viewpoints that are automatically configured to improve safety and provide smooth operation. This real-time adaptive viewpoint system takes robot position, orientation, and 3D point-cloud information into account to modify the user’s viewpoint to maximize visibility. Our prototype uses simultaneous localization and mapping (SLAM) based reconstruction with an omnidirectional camera, and we use the resulting models as well as simulations in a series of preliminary experiments testing navigation of various structures. Results suggest that automatic viewpoint generation can outperform first- and third-person view interfaces for virtual teleoperators in terms of ease of control and accuracy of robot operation.
Multitissue analysis of exercise and metformin on doxorubicin-induced iron dysregulation
Authors: Mackay Amy D. , Marchant Erik D. , Munk Devin J. , Watt Richard K. , Hansen Jason M. , Thomson David M. , Hancock Chad R.
Published: March 2019

Doxorubicin (DOX) is an effective chemotherapeutic treatment with lasting side effects in heart and skeletal muscle. DOX is known to bind with iron, contributing to oxidative damage resulting in cardiac and skeletal muscle toxicity. However, major cellular changes to iron regulation in response to DOX are poorly understood in liver, heart, and skeletal muscle. Additionally, two cotreatments, exercise (EX) and metformin (MET), were studied for their effectiveness in reducing DOX toxicity by ameliorating iron dysregulation and preventing oxidative stress. The purposes of this study were to 1) characterize the DOX-induced changes of the major iron regulation pathway in liver, heart, and skeletal muscle and 2) to determine whether EX and MET exert their benefits by minimizing DOX-induced iron dysregulation. Mice were assigned to receive saline or DOX (15 mg/kg) treatments, paired with either EX (5 days) or MET (500 mg/kg), and were euthanized 3 days after DOX treatment. Results suggest that the cellular response to DOX is protective against oxidative stress by reducing iron availability. DOX increased iron storage capacity through elevated ferritin levels in liver, heart, and skeletal muscle. DOX reduced iron transport capacity through reduced transferrin receptor levels in heart and skeletal muscle. EX and MET cotreatments had protective effects in the liver through reduced transferrin receptor levels. At 3 days after DOX, oxidative stress was mild, as shown by normal glutathione and lipid peroxidation levels. Together these results suggest that the cellular response to reduce iron availability in response to DOX treatment is sufficient to match oxidative stress.
AMPK and PPARβ positive feedback loop regulates endurance exercise training-mediated GLUT4 expression in skeletal muscle
Authors: Koh Jin-Ho , Hancock Chad R. , Han Dong-Ho , Holloszy John O. , Nair K. Sreekumaran , Dasari Surendra
Published: March 2019

The objective of this study is to determine whether AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), or peroxisome proliferator-activated receptor β (PPARβ) can independently mediate the increase of glucose transporter type 4 (GLUT4) expression that occurs in response to exercise training. We found that PPARβ can regulate GLUT4 expression without PGC-1α. We also found AMPK and PPARβ are important for maintaining normal physiological levels of GLUT4 protein in the sedentary condition as well following exercise training. However, AMPK and PPARβ are not essential for the increase in GLUT4 protein expression that occurs in response to exercise training. We discovered that AMPK activation increases PPARβ via myocyte enhancer factor 2A (MEF2A), which acted as a transcription factor for PPARβ. Furthermore, exercise training increases the cooperation of AMPK and PPARβ to regulate glucose uptake. In conclusion, cooperation between AMPK and PPARβ via NRF-1/MEF2A pathway enhances the exercise training mediated adaptive increase in GLUT4 expression and subsequent glucose uptake in skeletal muscle.
Effects of Huanglian-Renshen-Decoction, a Fixed Mixture of Traditional Chinese Medicine, on the Improvement of Glucose Metabolism by Maintenance of Pancreatic β Cell Identity in db/db Mice
Authors: Yuan Fen , Wang Dingkun , Ma Leyi , Qin Xin , Gong Jing , Hu Meilin , Su Hao , Dong Hui , Lu Fuer
Published: March 2019

Huanglian-Renshen-Decoction (HRD) is widely used to treat type 2 diabetes mellitus (T2DM) in China. However, the underlying mechanism is unclear. We aimed to investigate the mechanism by which HRD regulates the glucose level. Forty 7-8-week-old db/db (BSK) mice were randomly assigned to the following four groups: model, low dose HRD (LHRD), high dose HRD (HHRD), and saxagliptin (SAX). Additionally, 10 db/m mice were assigned to control group. The experimental mice were administered 3.03g/kg/d and 6.06g/kg/d of HRD in the LHRD and HHRD groups, respectively, and 10mg/kg/d saxagliptin in the SAX group for 8 weeks. The control and model groups were supplied with distilled water. After the intervention, the pancreas and blood were collected and tested. Compared with that of model group, the fasting blood glucose (FBG) was significantly decreased in all intervention groups (p < 0.05 or 0.01), whereas fasting serum insulin (FINS) was increased significantly in both HHRD and SAX groups. The immunofluorescence images showed that the mass of insulin+ cells was increased and that of glucagon+ cells was reduced obviously in experimental groups compared to those of the model group. In addition, the coexpression of insulin, glucagon, and PDX1 was decreased in HHRD group, and the level of caspase 12 in islet was decreased significantly in all intervention groups. However, little difference was found in the number and morphology of islet, and the expression of ki67, bcl2, bax, caspase 3, and cleaved-caspase 3 in the pancreas among groups. Interestingly, the cleaved-Notch1 level was increased and the Ngn3 level in islet was decreased significantly in HHRD group. The HRD showed dose-dependent effects on glucose metabolism improvement through maintenance of β cell identity via a mechanism that might involve the Notch1/Ngn3 signal pathway in db/db mice.
Mongolian Medicine RuXian-I Treatment of Estrogen-Induced Mammary Gland Hyperplasia in Rats Related to TCTP Regulating Apoptosis
Authors: Zhang Jun-Fei , Liu Jia , Gong Guo-Hua , Zhang Bin , Wei Cheng-Xi
Published: March 2019

Mongolian medicine RuXian-I is composed of 30 Mongolian herbs, which is a traditional Mongolian recipe for clinical treatment of breast “Qi Su Bu Ri Le Du Sen” disease (hyperplasia of mammary glands, HMG). Based on the previous study, this dissertation further explores the therapeutic mechanism of RuXian-I on estrogen-induced HMG in rats. RuXian-I had no effect on the body weight and food intake of HMG rats and had no toxic effects on the five organs (heart, lung, spleen, and kidney). RuXian-I reduced the diameter and height of nipple, organ index, and pathological changes and alleviated the sex hormone levels oh HMG; RuXian-I reduced the upregulation of TCTP, Mcl-1, and Bcl-xL in breast tissue of mammary gland hyperplasia and increased the downregulation of p53, Bax, caspase-9, and caspase-3 protein. RuXian-I has an effective therapeutic activity on HMG rats, and its possible therapeutic mechanism is closely related to antiapoptosis protein TCTP-regulated apoptosis.
Development and Validation of the Dietary Habits and Colon Cancer Beliefs Survey (DHCCBS): An Instrument Assessing Health Beliefs Related to Red Meat and Green Leafy Vegetable Consumption
Authors: Smith Kristen S. , Raney Savannah V. , Greene Michael W. , Frugé Andrew D.
Published: March 2019

Dietary patterns characterized by higher red meat (RM) consumption are associated with increased colon cancer (CC) risk. Preclinical and epidemiological evidence suggest higher green leafy vegetable (GLV) consumption may mitigate these risks. Determining the relationship between dietary habits and expected health outcomes is needed.Methods. The Health Belief Model (HBM) was used to assess perceived CC susceptibility and severity, and related dietary benefits, barriers, and motivators. RM and GLV consumption were quantified using select DHQII items (n=15) capturing the previous 30 days’ intake. A 34-item Qualtrics survey was provided to a convenience sample of 1,075 adults residing throughout the US Confirmatory factor analysis measured fitness with HBM, and Cronbach’s alpha assessed subscale reliability. A subsample (n=47) completed a 2-week follow-up for test-retest reliability. Independent sample t-tests were used to compare RM and GLV intake and DHCCBS responses between genders. Individual barrier questions and RM and GLV consumption were compared using ANOVA for each gender; post hoc analyses between barrier question responses were assessed with Bonferroni correction. Results were considered significant with a p value of less than 0.05.Results. 990 US adults (52.7% female, 79.1% white, 50.8% aged 35+ years) completed valid surveys. Factor analysis with varimax rotation validated the construct of HBM subscales; only one question had a loading less than 0.745. Subscale Cronbach’s alphas ranged within 0.478-0.845. Overall test-retest reliability was acceptable (r=0.697, p=5.22x10−8). Participant BMI was (mean±SD) 26.7±6.6 kg/m2. Participants consumed (median, IQR) 2.3, 0.9-4.7 cooked cup equivalents GLV/week and 12.2, 5.8-21.5 ounces RM/week. Over half of respondents agreed or strongly agreed with the statement “I can’t imagine never eating red meat,” while less than one eighth of respondents agreed or strongly agreed with the statement “I don’t like the taste of green leafy vegetables.”Conclusion. The DHCCBS is a valid instrument for measuring health beliefs related to red meat, green leafy vegetables, and perceived colon cancer risk. Additionally, these findings suggest increasing GLV may be more feasible than reducing RM for CC risk reduction in meat eaters.
A Band That Causes Leaky Valves: Severe Mitral Regurgitation due to Left Atrial Fibrous Band—A Case Report and Literature Review
Authors: Nnaoma Christopher , Sandhu Gurdarshan , Sossou Christoph , Vavilin Ilan , Bustillo Jose , Garg Anshu
Published: March 2019

Left atrial fibrous band is a rare clinical and echocardiographic finding characterized by the presence of a fibrous band attached to the mitral valve. Diagnosis is accomplished with transesophageal echocardiography (TEE), live 3D imaging, or cardiac MRI. Most patients are asymptomatic and incidental findings. However, in rare cases, an atrial fibrous band can produce symptoms such as dyspnea on exertion, fatigue, and lightheadedness secondary to mitral regurgitation (MR) which can lead to heart failure if unattended to. More serious complications such as cardioembolic phenomenon can occur. We herein report a case of a 55-year-old male with hypertension who presented with dyspnea on exertion and chest pain. Transthoracic echocardiography (TTE) showed mitral valve prolapse with moderate to severe mitral regurgitation. TEE showed an atrial fibrous band. Given the patient’s poor exercise tolerance, he was taken to surgery for a mitral annuloplasty.
Network Pharmacology-Based Study on the Mechanism of Bushen-Jianpi Decoction in Liver Cancer Treatment
Authors: Wu Rong , Li Xiao-Yan , Wang Wen-Hai , Cai Fei-Fei , Chen Xiao-Le , Yang Meng-Die , Pan Qiu-Sha , Chen Qi-Long , Zhou Rong-Yao , Su Shi-Bing
Published: March 2019

To investigate the mechanism of a Bushen-Jianpi decoction (BSJPD) in liver cancer (LC) treatment, we analyzed clinical therapy data, conducted network pharmacology analysis, and performed pharmacological experimental verificationin vitroandin vivo. The univariate analysis of clinical therapy showed that the BSJPD was protective factor (p< 0.05). The network pharmacology analysis showed that 9 compounds were important nodes of BSJPD-LC therapy network. In experimental verification, the rate of apoptosis increased in the liver tumors of mice treated with the BSJPD (p< 0.05); drug serum with 20 % BSJPD inhibited cell viability (p< 0.05) and reduced the expression of PI3K, the Bcl-xL/BAD ratio, and the levels of p53 and p-Akt in HepG2 cells. Moreover, licochalcone A, alisol B, and hederagenin inhibited cell viability (p< 0.05), induced cell apoptosis (p< 0.01), reduced p-Akt levels, and increased cleaved-CASP3 (p< 0.05) and p53 expression levels in HepG2 cells. These data suggest that the BSJPD prolongs the survival of LC patients and induces apoptosis and that it may be associated with the regulation of PI3K, Akt, p53, CASP3, and Bcl-xL/BAD expression.
Genomics and Precision Medicine: Molecular Diagnostics Innovations Shaping the Future of Healthcare in Qatar
Authors: AL-Dewik Nader I. , Qoronfleh M. Walid
Published: March 2019

Unprecedented developments in genomics research and ancillary technologies are creating the potential for astonishing changes in both the healthcare field and the life sciences sector. The innovative genomics applications include the following: (1) embracing next generation sequencing (NGS) in clinical diagnostics setting (applying both whole genome and exome sequencing), (2) single cell sequencing studies, (3) quantifying gene expression changes (including whole transcriptome sequencing), (4) pharmacogenomics, and (5) cell-free DNA blood-based testing. This minireview describes the impact of clinical genomics disruptive innovations on the healthcare system in order to provide better diagnosis and treatment. The observed evolution is not limited to the point-of-care services. Genomics technological breakthroughs are pushing the healthcare environment towards personalized healthcare with the real potential to attain better wellbeing. In this article, we will briefly discuss the Gulf region population-based genome initiatives that intend to improve personalized healthcare by offering better prevention, diagnosis, and therapy for the individual (precision medicine). Qatar’s endeavor in genomics medicine will be underscored including the private Applied Biomedicine Initiative (ABI).
Inverse Occlusion: A Binocularly Motivated Treatment for Amblyopia
Authors: Zhou Jiawei , He Zhifen , Wu Yidong , Chen Yiya , Chen Xiaoxin , Liang Yunjie , Mao Yu , Yao Zhimo , Lu Fan , Qu Jia , Hess Robert F.
Published: March 2019

Recent laboratory findings suggest that short-term patching of the amblyopic eye (i.e., inverse occlusion) results in a larger and more sustained improvement in the binocular balance compared with normal controls. In this study, we investigate the cumulative effects of the short-term inverse occlusion in adults and old children with amblyopia. This is a prospective cohort study of 18 amblyopes (10-35 years old; 2 with strabismus) who have been subjected to 2 hours/day of inverse occlusion for 2 months. Patients who required refractive correction or whose refractive correction needed updating were given a 2-month period of refractive adaptation. The primary outcome measure was the binocular balance which was measured using a phase combination task; the secondary outcome measures were the best-corrected visual acuity which was measured with a Tumbling E acuity chart and converted to logMAR units and the stereoacuity which was measured with the Random-dot preschool stereogram test. The average binocular gain was 0.11 in terms of the effective contrast ratio (z=−2.344, p=0.019, 2-tailed related samples Wilcoxon Signed Rank Test). The average acuity gain was 0.13 logMAR equivalent (t17=4.76, p<0.001, 2-tailed paired samples t-test). The average stereoacuity gain was 339 arc seconds (z=−2.533, p=0.011). Based on more recent research concerning adult ocular dominance plasticity, we conclude that inverse occlusion in adults and old children with amblyopia does produce long-term gains to binocular balance and that acuity and stereopsis can improve in some subjects.
Acupuncture to Promote Recovery of Disorder of Consciousness after Traumatic Brain Injury: A Systematic Review and Meta-Analysis
Authors: Tan Li , Zeng Liling , Wang Ning , Deng Meijun , Chen Yinshi , Ma Tianyi , Zhang Luhan , Xu Zhenhua
Published: March 2019

Traumatic brain injury (TBI) has become an economic and social burden for patients and their families. While acupuncture is an effective tool for promoting recovery of disorder of consciousness (DOC) following TBI, there have been no comprehensive meta-analyses and/or systematic reviews addressing this topic. The present systematic review and meta-analysis aimed to assess the therapeutic efficacy of acupuncture for DOC after TBI. All randomized controlled trials (RCTs) incorporating acupuncture, or acupuncture combined with other interventions for DOC after TBI, were included and assessed by two independent investigators. Six outcome indicators were assessed: Glasgow Coma Scale (GCS); Glasgow Outcome Scale (GOS); mortality; efficacy rate; activities of daily living (ADL); and functional comprehensive assessment. Direct comparisons were performed using RevMan 5.3.0 software, with results presented as mean difference (MD) for continuous outcomes and relative risk (RR) for binary outcomes. A total of 3511 patients from 49 trials were included. Pooled analyses indicated that acupuncture may have a superior effect on GCS score (MD=2.03, 95% CI :1.92 2.43, Z=16.54, and P<0.00001); GOS score (RR=1.23, 95%CI: 1.18 1.35, Z=6.65, and P<0.00001); efficacy rate (RR=1.48, 95%CI: 1.40 1.56, Z=13.49, and P<0.00001); ADL (MD=9.20, 95% CI:8.19 10.21, Z=17.84, and P<0.00001); and mortality (RR=0.50, 95% CI:0.38 0.67, Z=4.70, and P<0.00001). The results demonstrated that the acupuncture group fared better than the control group in the treatment of DOC after TBI. However, studies were generally of poor quality, and publication bias favoring positive studies was obvious. Therefore, rigorous evaluation standards and well-designed studies are necessary in future studies.
Cellular Signaling in Müller Glia: Progenitor Cells for Regenerative and Neuroprotective Responses in Pharmacological Models of Retinal Degeneration
Authors: Liu Yang , Wang Chenguang , Su Guanfang
Published: March 2019

Retinal degenerative diseases are a leading cause of visual impairment or blindness. There are many therapies for delaying the progression of vision loss but no curative strategies currently. Stimulating intrinsic neuronal regeneration is a potential approach to therapy in retinal degenerative diseases. In contrast to stem cells, as embryonic/pluripotent stem cell-derived retinal progenitor cell or mesenchymal stem cells, Müller glia provided an endogenous cellular source for regenerative therapy in the retina. Müller glia are a major component of the retina and considerable evidence suggested these cells can be induced to produce the lost neurons in several species. Understanding the specific characteristic of Müller glia to generate lost neurons will inspire an attractive and alternative therapeutic strategy for treating visual impairment with regenerative research. This review briefly provides the different signal transduction mechanisms which are underlying Müller cell-mediated neuroprotection and neuron regeneration and discusses recent advances about regeneration from Müller glia-derived progenitors.
Research of Spatial and Temporal Evolution Mechanism and Countermeasures of Haze Spatial Pattern in China: Visual Field Based on Dynamic Evolution and Spatial Agglomeration
Authors: Tong Xin , Li Xuesen , Tong Lin , Chen Kai
Published: March 2019

In this paper, spatial domain verification of the haze of dependence and the dynamic evolution process of the spatial panel data model was based on the estimation of different factors that influence on the horizon haze effect and spillover effect from the perspective of spatial economics. The study found that the provincial space is dependent on Chinese haze; the influence of haze on neighboring provinces of the spatial spillover effect factors is obvious during the period of 2000∼2015; the effect of elastic coefficient of industrial structures on the haze near the space overflow area energy is high; thus the industrial structure has a significant inhibitory effect on the haze; the role of regional industrial transfer haze governance has been very fruitful; population, economic growth, financial development, and fiscal decentralization to reduce haze inhibiting the spillover effect of regional haze were increasing. In the formulation of haze-related policies and development planning, the government departments must take into account the spatial mechanism of regional haze and influencing factors and realize the overall reduction of haze amount in time dimension and spatial dimension in China.
Pharmacological Evaluation of Secondary Metabolites and Their Simultaneous Determination in the Arabian Medicinal Plant Plicosepalus curviflorus Using HPTLC Validated Method
Authors: Orfali Raha , Perveen Shagufta , Siddiqui Nasir Ali , Alam Perwez , Alhowiriny Tawfeq Abdullah , Al-Taweel Areej Mohammad , Al-Yahya Sami , Ameen Fuad , Majrashi Najwa , Alluhayb Khulud , Alghanem Bandar , Shaibah Hayat , Khan Shabana Iqrar
Published: March 2019

Plicosepalus is an important genus of the Loranthaceae family, and it is a semiparasitic plant grown in Saudi Arabia, traditionally used as a cure for diabetes and cancer in human and for increasing lactation in cattle. A flavonoid quercetin (P1), (-)-catechin (P2), and a flavane gallate 2S,3R-3,3′,4′,5,7-pentahydroxyflavane-5-O-gallate (P3) were isolated from the methanol extract of the aerial parts of P. curviflorus (PCME). The PCME and the isolated compounds were subjected to pharmacological assays to estimate peroxisome proliferator-activated receptors PPARα and PPARγ agonistic, anti-inflammatory, cytotoxic, and antimicrobial activities. Results proved for the first time the dual PPAR activation effect of the PCME and catechin (P2), in addition to the promising anti-inflammatory activity of the flavonoid quercetin (P1). Interestingly, both PCME and isolated compounds showed potent antioxidant activities while no antimicrobial effect against certain microbial strains had been reported from the extract and the isolated compounds. Based on the pharmacological importance of these compounds, an HPTLC validated method was developed for the simultaneous estimation of these compounds in PCME. It was found to furnish a compact and sharp band of compounds P1, P2, and P3 at Rf = 0.34, 0.47, and 0.65, respectively, using dichloromethane, methanol, and formic acid (90 : 9.5 : 0.5, (v/v/v)) as the mobile phase. Compounds P1, P2, and P3 were found to be 11.06, 10.9, 6.96 μg/mg, respectively, in PCME. The proposed HPTLC method offers a sensitive, precise, and specific analytical tool for the quantification of quercetin, catechin, and flavane gallates in P. curviflorus.
CholedochoClip: A Case of Obstructive Jaundice 14 Years after Cholecystectomy
Authors: Kim Grace E. , Morris John D. , Darwin Peter E.
Published: March 2019

Gallstone disease is a common gastrointestinal pathology that may result in surgical intervention. While cholecystectomy has relatively minimal risks, surgical clip migration is a rare complication that can cause severe morbidity and mortality. This report describes a rare phenomenon of a biliary stone forming onto a migrated surgical clip 14 years after cholecystectomy causing an obstructive jaundice. This case illustrates the importance of keeping a migrated surgical clip on the differential when encountering patients with symptoms of cholangitis after cholecystectomy.
Chronic NO Restriction in Hypertensive Rats Increases Abdominal but Not Thoracic Aortic Intrinsic Stiffness via an Augmentation in Profibrotic Materials
Authors: Lindesay George , Bézie Yvonnick , Ragonnet Christophe , Duchatelle Véronique , Isabelle Marc , Villeneuve Nicole , Vayssettes-Courchay Christine
Published: March 2019

The spontaneously hypertensive rat model with reduced NO synthesis (SHRLN) shares features with aging and hypertension in humans, among other a severe aortic stiffening. The present in vivo study aimed to compare thoracic (TA) and abdominal (AA) aortic stiffness in the SHRLN (treated 5 weeks with L-NAME), SHR, and normotensive Wistar Kyoto (WKY). Dynamic properties of TA and AA were measured in the same rats, using echotracking recording of aortic diameter coupled with blood pressure (BP). Measurements were performed first at operating BP and then after BP reduction in hypertensive rats, thus in isobaric conditions. Histological staining and immunohistochemistry were used for structural analysis at both sites. At operating pressure, BP and pulse pressure (PP) were higher in SHRLN compared with SHR. Stiffness index was also increased and distensibility decreased in both TA and AA in SHRLN. At WKY-matched blood pressure, isobaric AA parameters remained specifically altered in SHRLN, whereas TA recovered to values identical to WKYs. Collagen, fibronectin, α5-selectin, and FAK were increased in SHRLN compared with SHR or WKY. Nevertheless, only the strong accumulations of fibronectin and collagen at the AA site in SHRLN were associated with intrinsic stiffening. In conclusion, we confirm that NO restriction associated with hypertension induces a severe pathological phenotype and shows that L-NAME induced stiffening is more pronounced in AA than in TA as a result of greater fibrosis.
Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Siltuximab in High-Risk Smoldering Multiple Myeloma
Authors: Brighton Timothy A. , Khot Amit , Harrison Simon J. , Ghez David , Weiss Brendan M. , Kirsch Andres , Magen Hila , Gironella Mercedes , Oriol Albert , Streetly Matthew , Kranenburg Britte , Qin Xiang , Bandekar Rajesh , Hu Peter , Guilfoyle Mary , Qi Ming , Nemat Sepideh , Goldschmidt Hartmut
Published: March 2019

Purpose:

IL6 is important for the growth and survival of myeloma cells. This study evaluated blocking IL6 with siltuximab to delay the transition from high-risk smoldering multiple myeloma (SMM) to multiple myeloma.

Patients and Methods:

In a randomized, double-blind, placebo-controlled, multicenter study, 85 patients with high-risk SMM were randomized to 15 mg/kg siltuximab (43 patients) or placebo (42 patients). The primary endpoint was 1-year progression-free survival (PFS) rate, based on IMWG CRAB criteria. Secondary endpoints included progressive disease indicator rate, PFS, and safety.

Results:

Median age was 62 years (range: 21–84); 57% were male and 87% had a baseline Eastern Cooperative Oncology Group score of 0. The 1-year PFS rate was 84.5% (siltuximab) and 74.4% (placebo). After a median follow-up of 29.2 months, 32.6% of PFS events occurred with siltuximab and 42.9% with placebo. Median PFS was not reached with siltuximab but was 23.5 months with placebo [HR 0.50 (95% confidence interval, 0.24–1.04); P = 0.0597]. The safety profile of siltuximab was comparable with placebo. Most adverse events in the siltuximab group were grade 2/3; the most common serious adverse events were infections/infestations, and renal/urinary disorders. Mortality was low in both groups (3 deaths in the siltuximab group and 4 in the placebo group).

Conclusions:

Although this study did not meet the prespecified protocol hypothesis criteria, data suggest that siltuximab may delay the progression of high-risk SMM.
IL15 Enhances CAR-T Cell Antitumor Activity by Reducing mTORC1 Activity and Preserving Their Stem Cell Memory Phenotype
Authors: Alizadeh Darya , Wong Robyn A. , Yang Xin , Wang Dongrui , Pecoraro Joseph R. , Kuo Cheng-Fu , Aguilar Brenda , Qi Yue , Ann David K. , Starr Renate , Urak Ryan , Wang Xiuli , Forman Stephen J. , Brown Christine E.
Published: March 2019

Improvements in the quality and fitness of chimeric antigen receptor (CAR)-engineered T cells, through CAR design or manufacturing optimizations, could enhance the therapeutic potential of CAR-T cells. One parameter influencing the effectiveness of CAR-T cell therapy is the differentiation status of the final product: CAR-T cells that are less-differentiated and less exhausted are more therapeutically effective. In the current study, we demonstrate that CAR-T cells expanded in IL15 (CAR-T/IL15) preserve a less-differentiated stem cell memory (Tscm) phenotype, defined by expression of CD62L+CD45RA+ CCR7+, as compared with cells cultured in IL2 (CAR-T/IL2). CAR-T/IL15 cells exhibited reduced expression of exhaustion markers, higher antiapoptotic properties, and increased proliferative capacity upon antigen challenge. Furthermore, CAR-T/IL15 cells exhibited decreased mTORC1 activity, reduced expression of glycolytic enzymes and improved mitochondrial fitness. CAR-T/IL2 cells cultured in rapamycin (mTORC1 inhibitor) shared phenotypic features with CAR-T/IL15 cells, suggesting that IL15-mediated reduction of mTORC1 activity is responsible for preserving the Tscm phenotype. CAR-T/IL15 cells promoted superior antitumor responses in vivo in comparison with CAR-T/IL2 cells. Inclusion of cytokines IL7 and/or IL21 in addition to IL15 reduced the beneficial effects of IL15 on CAR-T phenotype and antitumor potency. Our findings show that IL15 preserves the CAR-T cell Tscm phenotype and improves their metabolic fitness, which results in superior in vivo antitumor activity, thus opening an avenue that may improve future adoptive T-cell therapies.
Freedom of Movement: Defining, Researching, and Designing the Components of a Healthy Learning Ecosystem
Authors: Pinkard Nichole
Published: March 2019

Advances in technology and the rise of interconnected devices have ushered in new ways of accessing, communicating, and showcasing that have the potential to help us reimagine education as a networked ecosystem, supporting learners and information to move freely across connected nodes including and beyond school. In this paper, I explore the idea of recognizing and designing for a healthy learning ecosystem that supports freedom of movement, supporting crossing physical boundaries of location, domain-specific boundaries of different topical areas, and conceptual boundaries of value and goodness of fit. The paper begins with a look of my own childhood, serving as both an example and metaphor for the idea of freedom of movement. I then share three design-based implementation initiatives from the Digital Youth Network to support freedom of movement. I close with a suggested framework for defining a healthy learning ecosystem, one that utilized existing infrastructure and sociotechnical systems to leverage movement within communities towards the goal of optimizing youth development.