bluuebunny/crossref_metadata_2025 huggingface dataset:
Facilitating the Dissemination of iCBT for the Treatment of Anxiety and Depression: A Feasibility Study
Authors: DaPonte Daniella , Talbot France , Titov Nickolai , Dear Blake F. , Hadjistavropoulos Heather D. , Hadjistavropoulos Thomas , Jbilou Jalila
Published: June 2018

Translating existing internet-based cognitive-behavioural therapy (iCBT), along with the use of transdiagnostic and self-guided formats, may prove to be a cost-effective option of disseminating iCBT. Only recently have encouraging findings been reported for a self-guided delivery. This study assessed the feasibility of a French and self-guided version of an existing English iCBT course, called the Wellbeing Course, for the treatment of anxiety and depression. Existing ICBT programs have not yet been delivered in French, although this language is spoken worldwide. Thirty-one participants were included in a single group pre-post open trial with a 3-month follow-up. Feasibility outcomes were attrition, treatment adherence, acceptability, and preliminary efficacy. Primary outcome measures were the Patient Health Questionnaire 9-item (PHQ-9) and the Generalised Anxiety Disorder 7-item (GAD-7). Nearly 75% of the participants completed the program. Over 80% of the participants provided posttreatment and follow-up data. All study completers reported that they would recommend the Wellbeing Course to a friend having similar problems. Significant reductions in symptoms of anxiety and depression were found following treatment, consistent with earlier studies. These preliminary findings support the use of the assessed strategies to facilitate the cross-cultural dissemination of iCBT for a more universal access to quality psychological care.
Linear and non-linear models for national health expenditures in the USA
Authors: Kroopnick Allan J.
Published: June 2018

In this brief Article, using the elementary theory of differential equations as well as some basic economic theory, we will develop several estimates for national health expenditures for the United States: one using a linear model and three using non-linear models. We will derive the nonlinear models first and then compare them to the linear one in order to see if they differ significantly. While these estimates are for the United States, the methods used here, because they are robust, could be used for any country. Statistical information may be obtained from the World Bank databases which store health statistics by country [1].

What we will do here is estimate the total health costs as a percentage of gross domestic product (GDP) if no further copayments are required. In other words, we are seeking to estimate the total cost of health care as a percentage of GDP when all health care costs are covered by insurance and government subsidy. Several models will be discussed here since such estimates may be made using a variety of assumptions. There is no ‘best’ model, although such a decision is possible when comparing the estimates to actual data.
Associations of trauma exposure and post-traumatic stress disorder with the activity of the renin–angiotensin–aldosterone-system in the general population
Authors: Terock Jan , Hannemann Anke , Janowitz Deborah , Freyberger Harald J. , Felix Stephan B. , Dörr Marcus , Nauck Matthias , Völzke Henry , Grabe Hans J.
Published: June 2018

Background

Previous studies suggested that exposure to traumatic events during childhood and adulthood and post-traumatic stress disorder (PTSD) are associated with a dysregulation of different neuroendocrine systems. However, the activity of the renin–angiotensin–aldosterone-system (RAAS) in relation to trauma/PTSD has been largely neglected.

Methods

Traumatization, PTSD, and plasma concentrations of renin and aldosterone were measured in 3092 individuals from the general population. Subgroups according to the status of traumatization (‘without trauma’; ‘trauma, without PTSD’, ‘PTSD’) were formed and compared regarding renin and aldosterone concentrations. Additionally, we calculated the associations between the number of traumata, renin, and aldosterone concentrations. Finally, associations of PTSD with renin/aldosterone levels were controlled for the number of traumata (‘trauma load’).

Results

Levels of renin, but not aldosterone, were increased in traumatized persons without PTSD (p= 0.02) and, even stronger, with PTSD (p< 0.01). Moreover, we found a dose–response relation between the number of traumata and renin levels (β= 0.065;p< 0.001). Regression analyses showed PTSD as a significant predictor of renin (β= 0.38;p< 0.01). This effect was only slightly attenuated when controlled for trauma load (β= 0.32;p< 0.01).

Conclusions

Our results suggest that traumatization has lasting and cumulative effects on RAAS activity. Finding elevated renin levels in PTSD independent from trauma load supports the concept of PTSD as a disorder with specific neuroendocrine characteristics. Alternatively, elevated renin levels in traumatized persons may increase the risk for developing PTSD. Our findings contribute to explain the relationship between traumatic stress/PTSD and physical disorders.
Symptomatic carotid stenosis and ipsilateral carotid body tumor
Authors: Shah Samir K. , Levine Seth , O’Leary James , Belkin Michael
Published: June 2018

Abstract. We report an unusual combination of a symptomatic carotid stenosis and ipsilateral carotid body tumor. This patient was successfully treated with simultaneous carotid endarterectomy and tumor resection. Following, the unique challenges and technique are discussed.
Context-based learning for Inhibition of alternative conceptions: the next step forward in science education
Authors: Renouard Alexandra , Mazabraud Yves
Published: June 2018

The scientific literacy level of the whole population has long been focusing the researchers’ attention because of its direct impact on many aspects of our lives. As a matter of fact, studies in cognition have both been inspired by educational issues as well as by misconceptions of scientific ideas often based on irrational beliefs, old theories, unscientific reasoning, or unassimilated conceptual instruction. As a result, individual conceptions are now accurately described in many scientific fields, which has led to improvements in science teaching and learning. However, the community (scientists, academics, high school and primary school teachers, and educators) has not yet succeeded in solving all the issues, so some pre-existing misconceptions still persist in the population. In this paper, we argue that cognition studies must now focus on the origin of individuals’ conceptions and on their modes of acquisition and propagation. The goal is to provide educational tools for acting upstream, during early scientific instruction, before the very acquisition of scientific conceptions.
Systems pharmacology using mass spectrometry identifies critical response nodes in prostate cancer
Authors: Ebhardt H. Alexander , Root Alex , Liu Yansheng , Gauthier Nicholas Paul , Sander Chris , Aebersold Ruedi
Published: June 2018

In the United States alone one in five newly diagnosed cancers in men are prostate carcinomas (PCa). Androgen receptor (AR) status and the PI3K-AKT-mTOR signal transduction pathway are critical in PCa. After initial response to single drugs targeting these pathways resistance often emerges, indicating the need for combination therapy. Here, we address the question of efficacy of drug combinations and development of resistance mechanisms to targeted therapy by a systems pharmacology approach. We combine targeted perturbation with detailed observation of the molecular response by mass spectrometry. We hypothesize that the molecular short-term (24 h) response reveals details of how PCa cells adapt to counter the anti-proliferative drug effect. With focus on six drugs currently used in PCa treatment or targeting the PI3K-AKT-mTOR signal transduction pathway, we perturbed the LNCaP clone FGC cell line by a total of 21 treatment conditions using single and paired drug combinations. The molecular response was analyzed by the mass spectrometric quantification of 52 proteins. Analysis of the data revealed a pattern of strong responders, i.e., proteins that were consistently downregulated or upregulated across many of the perturbation conditions. The downregulated proteins, HN1, PAK1, and SPAG5, are potential early indicators of drug efficacy and point to previously less well-characterized response pathways in PCa cells. Some of the upregulated proteins such as 14-3-3 proteins and KLK2 may be useful early markers of adaptive response and indicate potential resistance pathways targetable as part of combination therapy to overcome drug resistance. The potential of 14-3-3ζ (YWHAZ) as a target is underscored by the independent observation, based on cancer genomics of surgical specimens, that its DNA copy number and transcript levels tend to increase with PCa disease progression. The combination of systematic drug perturbation combined with detailed observation of short-term molecular response using mass spectrometry is a potentially powerful tool to discover response markers and anti-resistance targets.
Down-selection of the VAR2CSA DBL1-2 expressed in E. coli as a lead antigen for placental malaria vaccine development
Authors: Chêne Arnaud , Gangnard Stéphane , Dechavanne Célia , Dechavanne Sebastien , Srivastava Anand , Tétard Marilou , Hundt Sophia , Leroy Odile , Havelange Nicolas , Viebig Nicola K. , Gamain Benoît
Published: June 2018

Over 50 million women are exposed to the risk of malaria during pregnancy every year. Malaria during pregnancy is a leading global cause of maternal morbidity and adverse pregnancy outcomes. Adhesion of Plasmodium falciparum-infected erythrocytes to placental chondroitin-4-sulfate (CSA) has been linked to the severe disease outcome of placental malaria. Accumulated evidence strongly supports VAR2CSA as the leading placental malaria vaccine candidate. Recombinant proteins encompassing the VAR2CSA high affinity CSA binding site have been generated, and their activity as immunogens that elicit functional (inhibitory) and cross-reactive antibodies against CSA-binding parasites assessed. The expression of His-tagged proteins was compared in four different expression systems and their capacity to bind specifically to CSA was analyzed. CHO cells and E. coli SHuffle cells were the two expression systems able to express some of the recombinant proteins in reasonable amounts. Larger analytical scale production of DBL1x-2× (3D7) and DBL3x-4ε (FCR3) best expressed in CHO and E. coli SHuffle cells were performed. Purified proteins were administered to rats either alone or adjuvanted with human approved adjuvants. Analysis of the functionality and cross-reactivity of the induced antibodies allowed us to down-select the DBL1x-2(3D7) expressed in E. coli SHuffle cells as the best antigen to be transitioned to further clinical development in order to protect future pregnant women living in malaria endemic areas against the severe clinical outcomes of placental malaria.
Enhanced Delta-Notch Lateral Inhibition Model Incorporating Intracellular Notch Heterogeneity and Tension-Dependent Rate of Delta-Notch Binding that Reproduces Sprouting Angiogenesis Patterns
Authors: Koon Yen Ling , Zhang Songjing , Rahmat Muhammad Bakhait , Koh Cheng Gee , Chiam Keng-Hwee
Published: June 2018

Endothelial cells adopt unique cell fates during sprouting angiogenesis, differentiating into tip or stalk cells. The fate selection process is directed by Delta-Notch lateral inhibition pathway. Classical Delta-Notch models produce a spatial pattern of tip cells separated by a single stalk cell, or the salt-and-pepper pattern. However, classical models cannot explain alternative tip-stalk patterning, such as tip cells that are separated by two or more stalk cells. We show that lateral inhibition models involving only Delta and Notch proteins can also recapitulate experimental tip-stalk patterns by invoking two mechanisms, specifically, intracellular Notch heterogeneity and tension-dependent rate of Delta-Notch binding. We introduce our computational model and analysis where we establish that our enhanced Delta-Notch lateral inhibition model can recapitulate a greater variety of tip-stalk patterning which is previously not possible using classical lateral inhibition models. In our enhanced Delta-Notch lateral inhibition model, we observe the existence of a hybrid cell type displaying intermediate tip and stalk cells’ characteristics. We validate the existence of such hybrid cells by immuno-staining of endothelial cells with tip cell markers, Delta and CD34, which substantiates our enhanced model.
Estrogen promotes progression of hormone-dependent breast cancer through CCL2-CCR2 axis by upregulation of Twist via PI3K/AKT/NF-κB signaling
Authors: Han Rui , Gu Shanzhi , Zhang Yujiao , Luo Anqi , Jing Xin , Zhao Lin , Zhao Xinhan , Zhang Lingxiao
Published: June 2018

The chemokine (C-C motif) ligand 2 (CCL2) with its cognate receptor chemokine (C-C motif) receptor 2 (CCR2) plays important roles in tumor invasion and metastasis. However, the mechanisms and mediators for autocrine CCL2 and CCL2-CCR2 axis remain elusive in breast cancer. Here we examined the levels of CCL2 in 4 breast cancer cell lines along with 57 human breast cancer specimens and found them significantly increased with presence of 17β-estradiol (E2) in estrogen receptor (ER)-positive breast cancer cells, while anti-estrogen treatment weakened this enhancement. CCL2 expression positively correlated with Twist staining and aggressiveness of breast cancer. Estrogen exposure facilitated the proliferation, invasion and metastasis of hormone-dependent breast cancer and promoted angiogenesis via the increased secretion of CCL2in vitroandin vivo, which could be suppressed by disruption of CCL2-CCR2 axis with CCR2 antagonist RS102895. Knockdown of Twist in MCF-7 cells significantly inhibited E2-induced CCL2 production, indicating an essential role of Twist in CCL2 regulation under estrogenic condition. Our data show the hormonal regulation on CCL2-CCR2 axis is associated with enhanced Twist expression via activation of ERα and PI3K/AKT/NF-κB signaling. Thus, CCL2-CCR2 axis may represent as a novel therapeutic target eagerly needed for hormone-dependent breast cancer.
Combined effect of high hydrostatic pressure and ultraviolet radiation on quality parameters of refrigerated vacuum-packed tilapia (Oreochromis niloticus) fillets
Authors: Monteiro Maria Lúcia Guerra , Mársico Eliane Teixeira , Mano Sérgio Borges , da Silveira Alvares Thiago , Rosenthal Amauri , Lemos Mosar , Ferrari Elisa , Lázaro Cesar Aquiles , Conte-Junior Carlos Adam
Published: June 2018

This study investigated the effects of high hydrostatic pressure (HHP) and ultraviolet radiation (UV-C), individually and combined, on the physical, chemical and bacterial parameters of Nile tilapia (Oreochromis niloticus) fillets stored at 4 °C for 14 days. Tilapia fillets were divided into four groups: control (untreated samples), UV-C, HHP, and UV-C combined with HHP (UV-C+HHP); UV-C was applied at dose of 0.103 ± 0.002 J/cm2, and HHP at a pressure of 220 MPa for 10 min at 25 °C. All samples were analyzed for total aerobic mesophilic count (TAMC), total aerobic psychrotrophic count (TAPC), Enterobacteriaceae count, pH, lipid oxidation, total volatile basic nitrogen (TVB-N), ammonia (NH3), and biogenic amines. Although UV-C accelerated (P ≤ 0.05) the formation of cadaverine, both UV-C and HHP, alone or together, retarded bacterial growth and delayed the increase (P ≤ 0.05) in pH, TVB-N, NH3 and biogenic amines during refrigerated storage, extending the shelf life of refrigerated tilapia fillets at least 2.5 times considering the TAMC counts. Lipid oxidation was unaffected (P > 0.05) by UV-C radiation, and decreased (P ≤ 0.05) by HHP and UV-C+HHP. HHP alone or combined with UV-C showed higher potential benefits for tilapia fillets preservation considering the positive influence on cadaverine levels and lipid oxidation.
Use of hydrogen peroxide, citric acid and sodium hypochlorite as sanitizer for minimally processed table grapes
Authors: Ergun Muharrem , Dogan Ezgi
Published: June 2018

The objective of this study was to explore two local table grape cultivars, one is white and the other one red colored, as a minimally processed
produce, and to identify the most effective sanitizers (hydrogen peroxide, citric acid or sodium hypochlorite) to control microbial growth. The
table grape cultivars indigenous to Elazig province of Turkey ‘Agin Beyazi’ and ‘Agin Kirmizisi’ were tested in the present experiment. Grape
clusters were washed by dipping in tap water as control, in citric acid (20 g/L), with sodium hypochlorite (50 mg/L), or with hydrogen peroxide
(20 g/L), solutions for 1 minute. Grape berries were then placed into PET clamshells and kept at 4 °C for 10 days. The berries were subject to
quality assessments during the storage, and to total aerobic microbial and fungal count at the end. Washing with hydrogen peroxide- or sodium
hypochlorite-diluted water was very effective controlling both aerobic microbial and fungal growth. Citric acid treatment however represented no
significant effect on microbial growth. It is concluded that both hydrogen peroxide and sodium hypochlorite are strong sanitizers for table grapes
tested, with no detection of undesirable effects.
Stellenwert der matrixaugmentierten Knochenmarkstimulation in der Behandlung von Knorpelschäden des Kniegelenks: Konsensusempfehlungen der AG Klinische Geweberegeneration der DGOU
Authors: Niemeyer Philipp , Becher Christoph , Brucker Peter , Buhs Matthias , Fickert Stefan , Gelse Kolja , Günther Daniel , Kaelin Raphael , Kreuz Peter , Lützner Jörg , Nehrer Stefan , Madry Henning , Marlovits Stefan , Mehl Julian , Ott Henning , Pietschmann Matthias , Spahn Gunther , Tischer Thomas , Volz Martin , Walther Markus , Welsch Götz , Zellner Johannes , Zinser Wolfgang , Angele Peter
Published: June 2018

Für die operative Sanierung lokalisiert vollschichtiger Knorpelschäden der großen Gelenke stehen mit den Transplantationstechniken (autologe Knorpelzelltransplantation, autologe osteochondrale Transplantation) und knochenmarkstimulierenden Techniken unterschiedliche Therapieoptionen zur Verfügung. Vor allem für das Kniegelenk konnte aufgrund der verbesserten Studienlage das jeweils geeignete Anwendungsspektrum dieser Verfahren in letzter Zeit weiter präzisiert werden. Für die matrixaugmentierte Mikrofrakturierung als einzeitige Methode besteht jedoch noch keine genauere Indikationsabgrenzung, insbesondere auch nicht gegenüber den bereits etablierten Verfahren. In der vorliegenden Arbeit werden die derzeit für diese Methode zur Verfügung stehenden Biomaterialien und Anwendungsvarianten beschrieben und ihre präklinische und klinische Evidenz zusammengefasst. Grundsätzlich kann dabei festgestellt werden, dass sich die verschiedenen in diesem Bereich angebotenen Produkte hinsichtlich der Zahl und Qualität zugehöriger Studien (Evidenzlevel) noch erheblich voneinander unterscheiden. Um die matrixaugmentierte Mikrofrakturierung im Sinne einer ersten Indikationsempfehlung als Methode in den therapeutischen Algorithmus der knorpelrekonstruktiven Verfahren im Knie einzuordnen, wurde durch die Mitglieder der Arbeitsgemeinschaft (AG) Klinische Geweberegeneration der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie (DGOU) im Rahmen eines Konsensusprozesses eine Bewertung der verfügbaren Evidenz vorgenommen. Vor dem Hintergrund der aktuellen Datenlage wird ihre Anwendung derzeit im Grenzbereich zwischen Zelltransplantations- und knochenmarkstimulierenden Techniken sowie als Verbesserung der klassischen Mikrofrakturierung und überwiegend im Indikationsbereich der Mikrofrakturierung gesehen. Die Empfehlungen der AG haben vorläufigen und orientierenden Charakter und bedürfen einer erneuten Überprüfung nach Verbesserung der Studienlage.
Research Update: Bismuth-based perovskite-inspired photovoltaic materials
Authors: Lee Lana C. , Huq Tahmida N. , MacManus-Driscoll Judith L. , Hoye Robert L. Z.
Published: June 2018

Bismuth-based compounds have recently gained interest as solar absorbers with the potential to have low toxicity, be efficient in devices, and be processable using facile methods. We review recent theoretical and experimental investigations into bismuth-based compounds, which shape our understanding of their photovoltaic potential, with particular focus on their defect-tolerance. We also review the processing methods that have been used to control the structural and optoelectronic properties of single crystals and thin films. Additionally, we discuss the key factors limiting their device performance, as well as the future steps needed to ultimately realize these new materials for commercial applications.
Approximation of minimal surfaces with free boundaries: convergence results
Authors: Jenschke Tristan
Published: June 2018

In a previous paper we developed a penalty method to approximate solutions of the free boundary problem for minimal surfaces by solutions of certain variational problems depending on a parameter $\lambda $. There we showed existence and $C^2$-regularity of these solutions as well as convergence to the solution of the free boundary problem for $\lambda \to \infty $. In this paper we develop a fully discrete finite element procedure for approximating solutions of these variational problems and prove a convergence estimate, which includes an order of convergence with respect to the grid size.
Investigating consumer responses to online group buying service failures
Authors: Lin Hsin-Hui , Yen Wan-Chu , Wang Yi-Shun , Yeh Yen-Min
Published: June 2018

Purpose

The purpose of this paper is to explore the effects of consumer role (involved vs observing) on consumer responses in the context of online group buying (OGB) service failures.

Design/methodology/approach

A scenario simulation method with a 2×3 factorial design was used to investigate the impact of consumer role (i.e. involved consumers and observing consumers) on consumer responses (i.e. perceived quality, negative electronic word-of-mouth (eWOM), and switching intention). The moderating role of seller offering type (i.e. physical products, true services, and pseudo services) on the relationship between the consumer role and responses was also tested.

Findings

The differences in perceived quality, negative eWOM, and switching intention between involved consumers and observing consumers were significant. Further, seller offering type moderated the relationship between consumer role and consumer response.

Practical implications

These findings provide several important theoretical and practical implications in regard to OGB service failure and recovery.

Originality/value

This study enriches OGB and service failure literature by a pioneering investigation of how consumer roles respond to OGB service failures and how different seller offering types influence the relationship between consumer role and consumer response. The results will help service providers of OGB benefit from enhancing their service recovery strategies to cope with OGB service failures.
Post-harvest malpractices in fresh fruits and vegetables: food safety and health issues in India
Authors: Panghal Anil , Yadav D.N. , Khatkar Bhupender S. , Sharma Himanshu , Kumar Vikas , Chhikara Navnidhi
Published: June 2018

Purpose

Fruits and vegetables, being good source of energy, health promoting and protecting compounds with unique taste and flavor, are attracting consumers since ages. These horticultural produces start deterioration just after harvest; therefore, their proper storage is must during transportation and storage to retain maximum quality parameters and for good market value. Best storage conditions are required to prevent growth of micro flora and to maintain the nutritional values of harvested produce. Retailers and processors in every corner of world want to move toward the cheaper ways to increase the shelf life and texture of horticultural crops for better consumer preference. The purpose of this paper is to make consumers and researchers aware about different post harvest malpractices in fresh fruits and vegetables.

Design/methodology/approach

Lot of chemicals like colors, artificial ripening agents, sweeteners and waxes are applied on surface of horticulture produce to siphon off money from consumers, and these have adverse health effects directly or indirectly. Various regulatory agencies have launched various programs, acts and laws for monitoring and avoiding such unhealthy ways. Regulatory bodies launched training programs also for the food handlers and consumers to ensure the food safety from farm to fork.

Findings

This paper will throw light on different malpractices followed by retailers to manipulate the quality which causes adverse health effects and to create consumer awareness regarding such malpractices.

Originality/value

The paper emphasizes on current malpractices followed by retailers to mislead the consumers about fruits’ and vegetable’ quality by using sweeteners, colors and other chemical. On prolonged consumption, such substances lead to major health issues such as attention disorder.
Acupuncture and herbal formulation compared with artificial tears alone: evaluation of dry eye symptoms and associated tests in randomised clinical trial
Authors: Tong Louis , Htoon Hla Myint , Hou Aihua , Acharya Rajendra Udyavara , Tan Jen-Hong , Wei Qi-Ping , Lim Pat
Published: June 2018

Objective

Dry eye is a common disease with great health burden and no satisfactory treatment. Traditional Chinese medicine, an increasingly popular form of complementary medicine, has been used to treat dry eye but studies have been inconclusive. To address this issue, we conducted a randomised investigator-masked study which included the robust assessment of disease mechanisms.

Methods and analysis

Eligible participants (total 150) were treated with artificial tear (AT) alone, with added eight sessions of acupuncture (AC) or additional daily oral herb (HB) over a month.

Results

Participants treated with AC were more likely to respond symptomatically than those on AT (88% vs 72%, p=0.039) with a difference of 16% (95% CI: 0.18 to 31.1). The number-to-treat with AC to achieve response in one person was 7 (3 to 157). Participants in the AC group also had reduced conjunctival redness (automatic grading with Oculus keratograph) compared with AT (p=0.043) and reduced tear T helper cell (Th1)-cytokine tumour necrosis factor α (p=0.027) and Th2-cytokine interleukin 4 concentrations (p=0.038). AC was not significantly superior to AT in other outcomes such as tear osmolarity, tear evaporation rates, corneal staining and tear break-up times. No significant adverse effects were encountered. HB was not significantly different in the primary outcome from AT (80% vs 72%, p=0.26).

Conclusions

AC is safe and provides additional benefit in mild to moderate dry eye up to 1 month, compared with ATs alone. Treatment is associated with demonstrable molecular evidence of reduced inflammation. Provided that suitably qualified practitioners are available to implement standardised treatment, AC may be recommended as adjunctive therapy to AT.

Trial registration number

ClinicalTrials.gov (NCT02219204)registered on 14 August 2014.
A propensity matched analysis of robotic, minimally invasive, and conventional mitral valve surgery
Authors: Hawkins Robert B , Mehaffey J Hunter , Mullen Matthew G , Nifong Wiley L , Chitwood W Randolph , Katz Marc R , Quader Mohammed A , Kiser Andy C , Speir Alan M , Ailawadi Gorav
Published: June 2018

Objectives

Institutional studies suggest robotic mitral surgery may be associated with superior outcomes. The objective of this study was to compare the outcomes of robotic, minimally invasive (mini), and conventional mitral surgery.

Methods

A total of 2300 patients undergoing non-emergent isolated mitral valve operations from 2011 to 2016 were extracted from a regional Society of Thoracic Surgeons database. Patients were stratified by approach: robotic (n=372), mini (n=576) and conventional sternotomy (n=1352). To account for preoperative differences, robotic cases were propensity score matched (1:1) to both conventional and mini approaches.

Results

The robotic cases were well matched to the conventional (n=314) and mini (n=295) cases with no significant baseline differences. Rates of mitral repair were high in the robotic and mini cohorts (91%), but significantly lower with conventional (76%, P<0.0001) despite similar rates of degenerative disease. All procedural times were longest in the robotic cohort, including operative time (224 vs 168 min conventional, 222 vs 180 min mini; all P<0.0001). The robotic approach had comparable outcomes to the conventional approach except there were fewer discharges to a facility (7% vs 15%, P=0.001) and 1 less day in the hospital (P<0.0001). However, compared with the mini approach, the robotic approach had more transfusions (15% vs 5%, P<0.0001), higher atrial fibrillation rates (26% vs 18%, P=0.01), and 1 day longer average hospital stay (P=0.02).

Conclusion

Despite longer procedural times, robotic and mini patients had similar complication rates with higher repair rates and shorter length of stay metrics compared with conventional surgery. However, the robotic approach was associated with higher atrial fibrillation rates, more transfusions and longer postoperative stays compared with minimally invasive approach.
Osteoporosis in psoriatic arthritis: a cross-sectional study of an outpatient clinic population
Authors: Gulati Agnete Malm , Michelsen Brigitte , Diamantopoulos Andreas , Grandaunet Berit , Salvesen Øyvind , Kavanaugh Arthur , Hoff Mari , Haugeberg Glenn
Published: June 2018

Background

The risk of osteoporosis in patients with psoriatic arthritis (PsA) still remains unclear. The aim of this study was to investigate bone mineral density (BMD) at the hip and lumbar spine measured by dual-energy X-ray absorptiometry in patients with PsA.

Methods

From an outpatient clinic in southern Norway, 140 patients with PsA were consecutively recruited and assessed for osteoporosis as part of a prospective study from January 2013 to May 2014. An extensive data collection was performed including demographic data and measures reflecting disease activity and health status.

Results

Mean age was 52.4 years and 71 (50.7%) were women. Median disease duration was 7.8 years. The proportion of patients with low BMD (defined as Z score≤−1.0 SD) was comparable to the expected value of 16%, according to the normal distribution of the Z score in the population. Osteoporosis was only found in 6.4% (95% CI3% to 11%) of the patients. No significant associations were found between BMD and disease activity measures.

Conclusion

The prevalence of PsA patients with osteoporosis or low BMD was low and in the range seen in the reference population. This supports that patients with PsA are not at high risk for osteoporosis compared with the general population. Therefore, clinicians may follow the general population guidelines for monitoring of osteoporosis for patients with PsA.
Effect of three types of horseshoes and unshod feet on selected non‐podal forelimb kinematic variables measured by an extremity mounted inertial measurement unit sensor system in sound horses at the trot under conditions of treadmill and soft geotextile surface exercise
Authors: Stutz Joëlle Christina , Vidondo Beatriz , Ramseyer Alessandra , Maninchedda Ugo Ettore , Cruz Antonio M
Published: June 2018

Therapeutic farriery is part of the management of certain orthopaedic conditions. Non‐podal parameters are important as most horses shod with therapeutic shoes are expected to perform again and the choice of shoe type may be influenced by the effects they may have on gait. The aim of this prospective study was to evaluate the effects of three different shoe designs and unshod front feet on forelimb non‐podal kinematic variables using an extremity mounted inertial measurement unit (IMU) system under conditions of treadmill and overground exercise on a soft geotextile surface at the trot. Ten sound horses with no underlying orthopaedic problem were instrumented with eight IMUs at distal radii, tibia and third metacarpal/tarsal regions. Measurements were performed during four consecutive days. During the first three days, the three shoe types were randomly selected per horse and day. On the fourth day, all horses were tested unshod. Data were collected at the trot on a treadmill, and on a soft geotextile surface. Specifically designed software and a proprietary algorithm processed the accelerometer and gyroscope signals to obtain orientation and temporal data to describe selected kinematic variables predetermined by the system. Repeated‐measures analysis of variance (ANOVA) was used to assess differences between shoe type and surface. The presence of shoes produced significant changes in spatiotemporal variables which seemed to be related to shoe mass rather than shoe design as there were no significant differences found between different shoe types. Shod horses showed a gait characterised by an increased range of motion (ROM) of the fore limbs. Previously reported effects of the investigated shoes on podal kinematics do not seem to affect the investigated kinematic variables indicating perhaps a compensatory effect occurring at some level in the extremity.
Fission and fusion interaction phenomena of the discrete kink multi-soliton solutions for the Chen–Lee–Liu lattice equation
Authors: Liu Nan , Wen Xiao-Yong , Liu Yaqing
Published: June 2018

Chen–Lee–Liu (CLL) lattice equation is an integrable discretization of the CLL equation which can be used to model the evolution of the self-steepening optical pulses without self-phase modulation. In this paper, the discrete N-fold Darboux transformation (DT) is used to derive the discrete kink multi-soliton solutions in terms of determinant for CLL lattice equation. Soliton fission and fusion interaction structures of such solutions are shown graphically. The details of their evolution are investigated by using numerical simulations, showing that a small noise with amplitude less than or equal to 0.01 produces a strong oscillation and instability of these kink soliton solutions. The discrete generalized perturbation [Formula: see text]-fold DT is constructed to express some rational solutions in terms of the determinants of CLL lattice equation by modifying the discrete N-fold DT. Infinitely many conservation laws for CLL lattice equation are constructed based on its Lax representation. Results in this paper might be helpful for understanding the propagation of optical pulses.
Enhanced Indexing and Querying of Trajectories in Road Networks via String Algorithms
Authors: Koide Satoshi , Tadokoro Yukihiro , Yoshimura Takayoshi , Xiao Chuan , Ishikawa Yoshiharu
Published: June 2018

In this article, we propose a novel indexing and querying method for trajectories constrained in a road network. We aim to provide efficient algorithms for various types of spatiotemporal queries that involve routing in road networks, such as (1) finding moving objects that have traveled along a given path during a given time interval, (2) extracting all paths traveled after a given spatiotemporal context, and (3) enumerating all paths between two locations traveled during a certain time interval. Unlike the existing methods in spatial database research, we employ indexing techniques and algorithms from string processing. This idea is based on the fact that we can represent spatial paths as strings, because trajectories in a network are represented as sequences of road segment IDs. The proposed SNT-index (suffix-array-based network-constrained trajectory index) introduces two novel concepts to trajectory indexing. The first is FM-index, which is a compact in-memory data structure for pattern matching. The second is an inverse suffix array, which allows the FM-index to be integrated with the temporal information stored in a forest of B
+
-trees. Thanks to these concepts, we can reduce the number of B
+
-tree accesses required by the query processing algorithms to a constant number, something that cannot be achieved with existing methods. Although an FM-index is essentially a static index, we also propose a practical method of appending new data to the index. Finally, experiments show that our method can process the target queries for more than 1 million trajectories in a few tens of milliseconds, which is significantly faster than what the baseline algorithms can achieve without string algorithms.
Enhancement of Peptide Vaccine Immunogenicity by Increasing Lymphatic Drainage and Boosting Serum Stability
Authors: Moynihan Kelly D. , Holden Rebecca L. , Mehta Naveen K. , Wang Chensu , Karver Mark R. , Dinter Jens , Liang Simon , Abraham Wuhbet , Melo Mariane B. , Zhang Angela Q. , Li Na , Gall Sylvie Le , Pentelute Bradley L. , Irvine Darrell J.
Published: June 2018

Antitumor T-cell responses have the potential to be curative in cancer patients, but the induction of potent T-cell immunity through vaccination remains a largely unmet goal of immunotherapy. We previously reported that the immunogenicity of peptide vaccines could be increased by maximizing delivery to lymph nodes (LNs), where T-cell responses are generated. This was achieved by conjugating the peptide to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG (DSPE-PEG) to promote albumin binding, which resulted in enhanced lymphatic drainage and improved T-cell responses. Here, we expanded upon these findings and mechanistically dissected the properties that contribute to the potency of this amphiphile-vaccine (amph-vaccine). We found that multiple linkage chemistries could be used to link peptides with DSPE-PEG, and further, that multiple albumin-binding moieties conjugated to peptide antigens enhanced LN accumulation and subsequent T-cell priming. In addition to enhancing lymphatic trafficking, DSPE-PEG conjugation increased the stability of peptides in serum. DSPE-PEG peptides trafficked beyond immediate draining LNs to reach distal nodes, with antigen presented for at least a week in vivo, whereas soluble peptide presentation quickly decayed. Responses to amph-vaccines were not altered in mice deficient in the albumin-binding neonatal Fc receptor (FcRn), but required Batf3-dependent dendritic cells (DCs). Amph-peptides were processed by human DCs equivalently to unmodified peptides. These data define design criteria for enhancing the immunogenicity of molecular vaccines to guide the design of next-generation peptide vaccines. Cancer Immunol Res; 6(9); 1025–38. ©2018 AACR.
Unusual Cause of Gastrointestinal Bleeding in a Patient with Turner Syndrome
Authors: D’Incao Rafael Bergesch , Appel-da-Silva Marcelo Campos , Marcon Patricia dos Santos , Correa Eduardo Marques , Manenti Euler , Corso Carlos Otávio
Published: June 2018

Turner syndrome is an exclusively female genetic disease caused by complete or partial absence of the second X chromosome. It is classically characterized by congenital lymphedema, short stature, and gonadal dysgenesis. In addition, the syndrome is associated with several other abnormalities. One of them is gastrointestinal bleeding, which is frequently associated with inflammatory bowel disease, but it can also be caused by vascular lesions such as hemangioma, vascular ectasia, and telangiectasia. We report the case of a patient with Turner syndrome with an episode of gastrointestinal bleeding, outlining our pathway for the investigation and treatment of this condition.
Abdominoperineal Resection for Unexpected Distal Intramural Spreading of Rectal Cancer
Authors: Munakata Shinya , Murai Yuta , Koizumi Akihiro , Kato Hisaki , Yamamoto Riku , Ueda Syuhei , Tokuda Satoshi , Sakuraba Syunsuke , Kushida Tomoyuki , Orita Hajime , Sakurada Mutsumi , Maekawa Hiroshi , Sato Koichi , Wada Ryo
Published: June 2018

Introduction: In rectal cancer, distal intramural spread may sometimes occur, but a maximum extent of distal spread of > 6 cm is very rare. Case Presentation: A 65-year-old Japanese male with an advanced rectal cancer tumor with para-aortic lymph node metastasis was admitted. We performed a low anterior resection with lymphadenectomy, but the intraoperative frozen-section analysis of margins revealed malignant cell positivity; we, therefore, performed an abdominoperineal resection. Pathological findings showed that the maximum extent of distal spread was 6 cm. After 12 courses of FOLFOX4 as adjuvant chemotherapy, abdominal computed tomography revealed whole lymph node metastases, including Virchow’s node. Though FOLFIRI + panitumumab was started, he was not eligible for additional chemotherapy after 10 cycles. Conclusion: An intraoperative frozen pathology examination was helpful for the additional resection, when unexpected distal spreading had occurred in rectal cancer. The evidence of a distal negative margin should not be underestimated.
Rapid Electrical Stimulation Increased Cardiac Apoptosis Through Disturbance of Calcium Homeostasis and Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Geng Le , Wang Zidun , Cui Chang , Zhu Yue , Shi Jiaojiao , Wang Jiaxian , Chen Minglong
Published: June 2018

Background/Aims: Heart failure induced by tachycardia, the most common arrhythmia, is frequently observed in clinical practice. This study was designed to investigate the underlying mechanisms. Methods: Rapid electrical stimulation (RES) at a frequency of 3 Hz was applied on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for 7 days, with 8 h/day and 24 h/day set to represent short-term and long-term tachycardia, respectively. Age-matched hiPSC-CMs without electrical stimulation or with slow electrical stimulation (1 Hz) were set as no electrical stimulation (NES) control or low-frequency electrical stimulation (LES) control. Following stimulation, JC-1 staining flow cytometry analysis was performed to examine mitochondrial conditions. Apoptosis in hiPSC-CMs was evaluated using Hoechst staining and Annexin V/propidium iodide (AV/PI) staining flow cytometry analysis. Calcium transients and L-type calcium currents were recorded to evaluate calcium homeostasis. Western blotting and qPCR were performed to evaluate the protein and mRNA expression levels of apoptosis-related genes and calcium homeostasis-regulated genes. Results: Compared to the controls, hiPSC-CMs following RES presented mitochondrial dysfunction and an increased apoptotic percentage. Amplitudes of calcium transients and L-type calcium currents were significantly decreased in hiPSC-CMs with RES. Molecular analysis demonstrated upregulated expression of Caspase3 and increased Bax/Bcl-2 ratio. Genes related to calcium re-sequence were downregulated, while phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) was significantly upregulated following RES. There was no significant difference between the NES control and LES control groups in these aspects. Inhibition of CaMKII with 1 µM KN93 partly reversed these adverse effects of RES. Conclusion: RES on hiPSC-CMs disturbed calcium homeostasis, which led to mitochondrial stress, promoted cell apoptosis and caused electrophysiological remodeling in a time-dependent manner. CaMKII played a central role in the damages induced by RES, pharmacological inhibition of CaMKII activity partly reversed the adverse effects of RES on both structural and electrophysiological properties of cells.
Determining the Pathogenicity of a Genomic Variant of Uncertain Significance Using CRISPR/Cas9 and Human-Induced Pluripotent Stem Cells
Authors: Ma Ning , Zhang Joe Z. , Itzhaki Ilanit , Zhang Sophia L. , Chen Haodong , Haddad Francois , Kitani Tomoya , Wilson Kitchener D. , Tian Lei , Shrestha Rajani , Wu Haodi , Lam Chi Keung , Sayed Nazish , Wu Joseph C.
Published: June 2018

Background:

The progression toward low-cost and rapid next-generation sequencing has uncovered a multitude of variants of uncertain significance (VUS) in both patients and asymptomatic “healthy” individuals. A VUS is a rare or novel variant for which disease pathogenicity has not been conclusively demonstrated or excluded, and thus cannot be definitively annotated. VUS, therefore, pose critical clinical interpretation and risk-assessment challenges, and new methods are urgently needed to better characterize their pathogenicity.

Methods:

To address this challenge and showcase the uncertainty surrounding genomic variant interpretation, we recruited a “healthy” asymptomatic individual, lacking cardiac-disease clinical history, carrying a hypertrophic cardiomyopathy (HCM)-associated genetic variant (NM_000258.2:c.170C>A, NP_000249.1:p.Ala57Asp) in the sarcomeric gene
MYL3
, reported by the ClinVar database to be “likely pathogenic.” Human-induced pluripotent stem cells (iPSCs) were derived from the heterozygous VUS
MYL3
(170C>A)
carrier, and their genome was edited using CRISPR/Cas9 to generate 4 isogenic iPSC lines: (1) corrected “healthy” control; (2) homozygous VUS
MYL3
(170C>A
)
; (3) heterozygous frameshift mutation
MYL3
(170C>A/fs
)
; and (4) known heterozygous
MYL3
pathogenic mutation (NM_000258.2:c.170C>G), at the same nucleotide position as VUS
MYL3
(170C>A)
, lines. Extensive assays including measurements of gene expression, sarcomere structure, cell size, contractility, action potentials, and calcium handling were performed on the isogenic iPSC-derived cardiomyocytes (iPSC-CMs).

Results:

The heterozygous VUS
MYL3
(170C>A)
-iPSC-CMs did not show an HCM phenotype at the gene expression, morphology, or functional levels. Furthermore, genome-edited homozygous VUS
MYL3
(170C>A)
- and frameshift mutation
MYL3
(170C>A/fs)
-iPSC-CMs lines were also asymptomatic, supporting a benign assessment for this particular
MYL3
variant. Further assessment of the pathogenic nature of a genome-edited isogenic line carrying a known pathogenic
MYL3
mutation,
MYL3
(170C>G)
, and a carrier-specific iPSC-CMs line, carrying a
MYBPC3
(961G>A)
HCM variant, demonstrated the ability of this combined platform to provide both pathogenic and benign assessments.

Conclusions:

Our study illustrates the ability of clustered regularly interspaced short palindromic repeats/Cas9 genome-editing of carrier-specific iPSCs to elucidate both benign and pathogenic HCM functional phenotypes in a carrier-specific manner in a dish. As such, this platform represents a promising VUS risk-assessment tool that can be used for assessing HCM-associated VUS specifically, and VUS in general, and thus significantly contribute to the arsenal of precision medicine tools available in this emerging field.