bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-analysis of completion lymph node dissection in sentinel lymph node-positive melanoma
Authors: Angeles C V , Kang R , Shirai K , Wong S L
Published: March 2019

Background

The role of completion lymph node dissection (CLND) in patients with sentinel lymph node (SLN)-positive melanoma continues to be debated. This systematic review and meta-analysis evaluated survival and recurrence rate in these patients who underwent CLND, compared with observation.

Methods

A comprehensive MEDLINE and Embase database search was performed for cohort studies and RCTs published between January 2000 and June 2017 that assessed the outcomes of CLND compared with observation in patients with SLN-positive melanoma. The primary outcome was survival and the secondary outcome was recurrence rate. Studies were assessed for quality using the Cochrane risk-of-bias tool for RCTs and Newcastle–Ottawa Scale for cohort studies. Pooled relative risk or hazard ratio with 95 per cent confidence intervals were calculated for each outcome. The extent of heterogeneity between studies was assessed with the I2 test. The protocol was registered in PROSPERO (CRD42017070152).

Results

Fifteen studies (13 cohort studies with 7868 patients and 2 RCTs with 2228 patients) were identified for qualitative synthesis. Thirteen studies remained for quantitative meta-analysis. Survival was similar in patients who underwent CLND and those who were observed (risk ratio (RR) for death 0·85, 95 per cent c.i. 0·71 to 1·02). The recurrence rate was also similar (RR 0·91, 0·79 to 1·05).

Conclusion

Patients with SLN-positive melanoma do not have a significant benefit in survival or recurrence rate if they undergo CLND rather than observation.
The human ATF1 rs11169571 polymorphism associated with risk of nasopharyngeal carcinoma in Southern Chinese populations
Authors: Peng Shutang , Huang Guo‐Liang , Xu Nansong , Lu Yan , Zeng Liuyan , Li Xin , Luo Shengqun , Lyu Xiaoming , Jiang Qiang , Li Tong , He Zhiwei
Published: March 2019

Our previous work reported activating transcription factor 1 (ATF1) is a promotive factor of nasopharyngeal carcinoma (NPC) tumorigenesis. This study is to further explore the association between the human ATF1 rs11169571 polymorphism and the risk of NPC occurrence. The association between ATF1 rs11169571 and risk of NPC occurrence was investigated in clinical samples of 560 patients and 661 controls obtained from southern China with high incidence of NPC. The genotypes were detected by PCR‐RFLP. The differential expression activity of alleles ‐T and ‐C was analyzed with CNE‐2 and C666‐1 cells by luciferase reporter assay. Our data suggested that the allelic frequency and genotypes were significantly different between patients and controls. Compared to the TT homozygote, the TC and CC genotypes have been shown to be significantly decreased in NPC patients (OR = 0.494, 95% CI = 0.387‐0.629, P < 0.001 and OR = 0.556, 95% CI = 0.364‐0.851, P = 0.007, respectively). Compared to the ‐T allele, the ‐C allele is a factor of decreased risk in NPC (OR = 0.642, 95% CI = 0.537‐0.767, P < 0.001). Luciferase reporter activity revealed that the ‐T allele confers a higher expression activity than the ‐C allele in CNE2 cells and C666‐1 cells. In conclusion, ATF1 rs11169571 which could affect the expression of ATF1 is associated with NPC risk.
g‐Wert Ermittlung innovativer großformatiger Membranelemente
Authors: Kersken Matthias , Sinnesbichler Herbert
Published: March 2019

Die moderne Architektur favorisiert großflächige innovative Fassadenlösungen für die es oftmals noch keine festgeschriebenen Berechnungsverfahren zur Bestimmung der Produktkennwerte gibt. Das Fraunhofer‐Institut für Bauphysik IBP hat mit dem kalorimetrischen Fassaden‐ und Dachprüfstand eine Freiland‐Versuchseinrichtung geschaffen, mit deren Hilfe die energetischen Eigenschaften großformatiger, transparenter Bauelemente unter realer Witterung messtechnisch untersucht und auf reproduzierbare, normkonforme g‐Werte zurückgeführt werden können. Dieser Beitrag stellt das Konzept der Prüfeinrichtung und die notwendigen statistischen Auswertemethoden vor. Beispielhaft für durchgeführte Messungen wird dieses Verfahren an ausgewählten Membranprüflingen demonstriert.
Entwicklung innovativer Mehrscheiben‐Isoliergläser mit Angriffhemmung
Authors: Weimar Thorsten , Vuylsteke Laura
Published: March 2019

Die aktuellen Vorgaben in der Energieeinsparverordnung an den Wärmeschutz führen zu einem erhöhten Bedarf an Dreischeiben‐Isoliergläsern in der Gebäudehülle. Im Vergleich zu Zweischeiben‐Isoliergläsern wird mit einem zusätzlichen Scheibenzwischenraum ein deutlich verbesserter Wärmedämmwert erzielt. Allerdings steigt auch mit zunehmender Anzahl der Glasschichten insbesondere bei Sicherheitssonderverglasungen das Eigengewicht. Der Einsatz von Polycarbonat im Querschnitt führt zu einem geringeren Eigengewicht, einer höheren Wärmedämmung und einer Verbesserung der Angriffhemmung. Die Entwicklung von innovativen Mehrscheiben‐Isoliergläsern aus Glas‐Polycarbonat‐Verbundtafeln erfolgt deshalb unter den drei Aspekten der Gewichtsreduzierung, Energieeinsparung und Angriffhemmung.
Zwei Stahl‐/Glasdächer in geometrischer Freiform – zwei unterschiedliche Herangehensweisen
Authors: Zimmermann Stefan , Schmitt Felix
Published: March 2019

Die Duale Hochschule Stuttgart überdacht das Atrium ihres Neubaus mit einem Stahl‐/Glasdach. In New York wird die historische „Tammany Hall” entkernt und renoviert. Auch dieses Gebäude wird mit einem Stahl‐/Glasdach überdacht. Bei beiden Dächern handelt es sich um Stab‐/Knotenkonstruktionen in geometrischer Freiform mit ungefähr gleicher Fläche. Die architektonischen und technischen Ansätze bei beiden Dächern weichen jedoch stark voneinander ab. Der Beitrag vergleicht die unterschiedliche Herangehensweise bei beiden Projekten, die sich durch verschiedene gestalterische Ansätze, andere technische Randbedingungen, abweichende terminliche Abläufe, differierende Kostenrahmen, kulturelle Unterschiede und verschiedene Abwicklungskonzepte in Deutschland und den USA ergeben.
Optimierung der entspiegelten Schutzverglasung vor Glasmalereien am Kölner Dom
Authors: Busse Felix , Huber Ulrich
Published: March 2019

Mit Fenstern aus sieben Jahrhunderten hat der Kölner Dom einen der größten Bestände historischer Glasmalerei weltweit. Diese sind in mehrfacher Hinsicht permanent gefährdet. Die Restaurierung hat nur dann eine dauerhafte Wirkung, wenn sie mit der Installation einer Schutzverglasung kombiniert wird, die vor Witterungseinflüssen schützt. Die Wahrnehmung von Schutzverglasungen wird wesentlich bestimmt durch die Intensität und Farbe der Reflexion des Lichtes an der Glasoberfläche. Wichtig ist dabei der jeweilige Betrachtungswinkel. Durch den Einsatz und die Optimierung eines interferenzoptischen Entspiegelungssystems kann die visuelle Wahrnehmung einer Schutzverglasung an historischen Gebäuden positiv beeinflusst werden.
The impact of changes in stakeholder salience on corporate social responsibility activities in Russian energy firms: A contribution to the divergence/convergence debate
Authors: Benyaminova Alina , Mathews Martin , Langley Paul , Rieple Alison
Published: March 2019

This empirical paper examines the drivers underpinning changes to socially responsible behaviours in the Russian energy sector. Responding to recent requests to contextualise corporate social responsibility (CSR) research, we focus on the changing set of stakeholders and developments in their saliency as reflected in corporations' CSR activities. Based on interviews with more than 30 industry professionals, our findings suggest that Russian energy companies' CSR is strongly stakeholder‐driven, and organisations adapt their activities according to their dependence on the resources that these salient stakeholders possess.

We challenge the proposition that CSR in Russia arises from purely endogenous, historical, paternalism, or neo‐paternalism. We identify stakeholders that now shape CSR in the Russian energy sector, both endogenous (institutional and contextual forces relevant to the national business system) and exogenous (relating to the organisational field of the energy industry—international by nature). We thereby contribute to the convergence/divergence debate within CSR theory by demonstrating that both national business systems and the organisational field must be taken into account when analysing the forces that shape CSR strategies in any one country.
Fine‐needle aspiration features of ossifying fibromyxoid tumor in the breast: A case report and literature review
Authors: Gajdzis Pawel , Laé Marick , Choussy Olivier , Lavigne Marion , Klijanienko Jerzy
Published: March 2019

Ossifying fibromyxoid tumor (OFT) is a very rare soft tissue tumor which is characterized by incomplete peripheral mature bone shell. To date, cytological features of OFT have been poorly studied with only seven case reports. In this study, an additional case of OFT investigated by fine‐needle aspiration is presented. A 75‐year‐old man with advanced nasopharyngeal carcinoma presented with peripherally calcified right breast mass. Smears were hypercellular and stroma‐rich. Tumor cells were mainly dispersed, with epithelioid morphology and eccentrically located nuclei. In the background, there was abundant eosinophilic myxoid secretion. No necrosis, atypia, or mitotic activity was found. The tumor showed diffuse S‐100, CD10, STAT6 expression and focal desmin, estrogen receptor (ER), and progesteron receptor (PgR) expression. Fluorescence in situ hybridization study revealed PHF1 rearrangement in 9% of cells. Cytological characteristic of OFT is quite distinctive and precise diagnosis can be made, especially when it is coupled with compatible radiological findings.
Detection of structured single‐strand DNA via solid‐state nanopore
Authors: Liu Shao‐Chuang , Li Qiao , Ying Yi‐Lun , Long Yi‐Tao
Published: March 2019

Nanopore is a single‐molecule analysis method which also employed electrophoresis has achieved promising single‐molecule detections. In this study, we designed two kinds of confined spaces by fabricating solid‐state nanopores with desirable diameters to study the structured single‐strand DNA of C‐rich quadruplex. For the nanopore whose diameter is larger than the quadruplex size, the DNA molecule could directly translocate through the nanopore with extremely high speed. For the nanopore whose diameter is smaller than the quadruplex size, DNA molecule which is captured by nanopore could return to the solution without translocation or unzip the quadruplex structure into single‐strand and then pass the nanopore. This study certifies that choosing a suitable sensing interface is the vital importance of observing detailed single‐molecule information. The solid‐state nanopores hold the great potential to study the structural dynamics of quadruplex DNA molecule.
Aluminum‐Catalyzed One‐Pot Synthesis of Polyester‐b‐Polypeptide Block Copolymers by Ring‐Opening Polymerization
Authors: Schmid Thibault E. , Robert Carine , Richard Vincent , Raman Sumesh K. , Guérineau Vincent , Thomas Christophe M.
Published: March 2019

Polypeptides are a class of important biomaterials that are extensively utilized in applications such as drug delivery systems, sensors, tissue engineering, biomimetic synthesis of ordered inorganic nanostructures, and catalysis. In particular, the association of polypeptides to polyesters in copolymer architectures provides versatile original materials. However, the catalytic formation of this type of peptide‐based copolymers remains a considerable synthetic challenge. Here, a new strategy to obtain copolymer materials by one‐pot catalysis is reported, which confers great interest to the approach.
A comparative study of Twitter utilization in disaster management between public and private organizations
Authors: Gunawong Panom , Thongpapanl Narongsak , Ferreira Caitlin C.
Published: March 2019

Twitter has become a commonly used platform by both public and private organizations to assist with the dissemination of information related to disaster management. This research makes use of a mixed‐method approach in determining the extent and manner in which Twitter is used to disseminate disaster management information by both public and private organizations. This research found that public organizations are bound by strict regulations resulting in a lower volume and smaller variety of disaster‐related information being disseminated. The nature of an organization and the processes of decision making therein are suggested to influence the ability of an organization to successfully use Twitter as an effective tool for disaster management. Organizations in Thailand currently underutilize Twitter for disaster management, as neither public nor private organizations use Twitter as a multidirectional communication disaster management tool.
Expression of tSTAT3, pSTAT3727, and pSTAT3705 in the epithelial cells of hormone‐naïve prostate cancer
Authors: Krzyzanowska Agnieszka , Don‐Doncow Nicholas , Marginean Felicia Elena , Gaber Alexander , Watson R. William , Hellsten Rebecka , Bjartell Anders
Published: March 2019

Background

The signal transducer and activator of transcription 3 (STAT3) pathway is observed to be constitutively activated in several malignancies including prostate cancer (PCa). In the present study, we investigated the expression of total STAT3 (tSTAT3) and two forms of activated phosphorylated STAT3 (pSTAT3727 and pSTAT3705) in tissue microarrays (TMA) of two cohorts of localized hormone‐naïve PCa patients and analyzed associations between the expression and disease outcome.

Methods

The expression of tSTAT3, pSTAT3727, and pSTAT3705 was scored in the nuclei and cytoplasm of prostatic gland epithelial cells in two TMAs of paraffin‐embedded prostatic tissue. The TMAs consisted of tissue originated from hormone‐naïve radical prostatectomy patients from two different sites: Malmö, Sweden (n = 300) and Dublin, Ireland (n = 99).

Results

The nuclear expression levels of tSTAT3, pSTAT3727, and pSTAT3705 in the epithelial cells of benign glands were significantly higher than in the cancerous glands. Cytoplasmic tSTAT3 levels were also higher in benign glands. Patients with low pSTAT3727 and pSTAT3705 levels in the cancerous glands showed reduced times to biochemical recurrence, compared with those with higher levels. No significant trends in nuclear nor in cytoplasmic tSTAT3 were observed in relation to biochemical recurrence in the Malmö cohort. Higher cytoplasmic tSTAT3 was associated with reduced time to biochemical recurrence in the Dublin cohort. Adding the tSTAT3 and pSTAT3 expression data to Gleason score or pathological T stage did not improve their prognostic values.

Conclusions

Low pSTAT3727 and pSTAT3705 expression in epithelial cells of cancerous prostatic glands in hormone‐naïve PCa was associated with faster disease progression. However, pSTAT3 and tSTAT3 expression did not improve the prognostic value of Gleason score or pathological T stage and may not be a good biomarker in the early hormone naïve stages of PCa.
High levels of PIWI‐interacting RNAs are present in the small RNA landscape of prostate epithelium from vitamin D clinical trial specimens
Authors: Baumann Bethany , Lugli Giovanni , Gao Shang , Zenner Morgan , Nonn Larisa
Published: March 2019

Background

Vitamin D, a hormone that acts through the nuclear vitamin D receptor (VDR), upregulates antitumorigenic microRNA in prostate epithelium. This may contribute to the lower levels of aggressive prostate cancer (PCa) observed in patients with high serum vitamin D. The small noncoding RNA (ncRNA) landscape includes many other RNA species that remain uncharacterized in prostate epithelium and their potential regulation by vitamin D is unknown.

Methods

Laser capture microdissection (LCM) followed by small‐RNA sequencing was used to identify ncRNAs in the prostate epithelium of tissues from a vitamin D‐supplementation trial. VDR chromatin immunoprecipitation‐sequencing was performed to identify vitamin D genomic targets in primary prostate epithelial cells.

Results

Isolation of epithelium by LCM increased sample homogeneity and captured more diversity in ncRNA species compared with publicly available small‐RNA sequencing data from benign whole prostate. An abundance of PIWI‐interacting RNAs (piRNAs) was detected in normal prostate epithelium. The obligate binding partners of piRNAs, PIWI‐like (PIWIL) proteins, were also detected in prostate epithelium. High prostatic vitamin D levels were associated with increased expression of piRNAs. VDR binding sites were located near several ncRNA biogenesis genes and genes regulating translation and differentiation.

Conclusions

Benign prostate epithelium expresses both piRNA and PIWIL proteins, suggesting that these small ncRNA may serve an unknown function in the prostate. Vitamin D may increase the expression of prostatic piRNAs. VDR binding sites in primary prostate epithelial cells are consistent with its reported antitumorigenic functions and a role in ncRNA biogenesis.
Electron Emission Mechanism of Heavily Phosphorus‐Doped Diamond with Oxidized Surface
Authors: Masuzawa Tomoaki , Neo Yoichiro , Mimura Hidenori , Okano Ken , Yamada Takatoshi
Published: March 2019

In this study, electron emission model is investigated for heavily phosphorus‐doped n‐type diamond having positive electron affinity surface. Ultraviolet photoelectron spectroscopy (UPS) is conducted to determine the band structure of the diamond. In addition, combined UPS and field‐emitted electron spectroscopy is carried out in order to determine the energy level, from which electrons are emitted. The combined spectroscopy suggests that electrons are emitted from the conduction band of the diamond, and the emission mechanism is dominated by electron tunneling through surface potential barrier.
Significantly Enhanced Performance of Triboelectric Nanogenerator by Incorporating BaTiO3 Nanoparticles in Poly(vinylidene fluoride) Film
Authors: Tao Xiang , Jin Hao , Ma Mengjuan , Quan Liwei , Chen Jinkai , Dong Shurong , Zhang He , Lv Chaofeng , Fu Yongqing , Luo Jikui
Published: March 2019

Triboelectric nanogenerators (TENGs) have received significant attention in recent years due to their renewable and sustainable properties. They convert mechanical energy into electric energy through contact and separation of two dissimilar materials. Many methods have been developed to improve the performance of TENGs, but little attention has been paid to use nanoparticles such as BaTiO3 (BTO) with high dielectric constant for enhancing the performance. This paper reports the achievement of significant performance enhancement of poly(vinylidene fluoride) (PVDF)/polyamide‐6 (PA6) TENGs by incorporating BTO nanoparticles into the PVDF film. The PVDF‐BTO/PA6 TENG with 10 wt% BTO nanoparticles shows the best results with a peak voltage and charge density up to 900 V and 34.4 μC m−2 at contact frequency of 5 Hz when the contact force and the spacer distance are 180 N and 100 mm, which are much higher than 384 V and 26.4 μC m−2 of the PVDF/PA6 TENG without incorporating BTO nanoparticles. Further increase in the BTO concentration deteriorates the output performance of the TENGs. Detailed investigations on the piezo‐response and permittivity of the PVDF‐BTO films show that the increased piezoelectric constant and permittivity are responsible for the significantly enhanced performance of the TENGs. A mathematical model has been developed to describe the output voltages of the TENG as a function of thickness of the PVDF‐BTO film.
Alkaloids from nux vomica suppresses colon cancer cell growth through Wnt/β‐catenin signaling pathway
Authors: Ren Hua , Zhao Jianping , Fan Dongsheng , Wang Ze , Zhao Tingjie , Li Yuejin , Zhao Yirui , Adelson David , Hao Huiqin
Published: March 2019

Brucine and Strychnine are alkaloids isolated from the seeds of Strychnos nux vomica L., which have long been used as a traditional medicine for the treatment of tumor. However, the effect of Brucine and Strychnine on colorectal cancer (CRC) and the underlying molecular mechanism remain unclear. In the present study, Brucine and Strychnine displayed profound inhibitory effects on the growth of human colon cancer cells. The results of flow cytometric analysis demonstrated that the two alkaloids induced cellular apoptosis. Moreover, the growth of DLD1 xenografted tumors in nude mice was significantly suppressed in the Brucine or Strychnine treated group. Mechanistically, the Wnt/β‐catenin is involved in this phenomenon, which is characterized by significantly increased expression of DKK1 and APC, whereas decreased expression of β‐catenin, c‐Myc, and p‐LRP6 in CRC cells as well as tumor tissues. Collectively, Brucine and Strychnine have targeted inhibition for colon cancer proliferation both in vitro and in vivo, and it is valuable for future exploitation and utilization as an antitumor agent of CRC.
Synthesis of Tertiary Aromatic Amides from Tertiary Benzylamines via TBAI/TBHP‐Mediated C‐N‐Bond Cleavage
Authors: Dai Feiyang , Yang Yuhang , Gu Jiajia , Fang Zheng , Yang Zhao , Liu Chengkou , He Wei , Zhu Ning , Lu Bushi , Guo Kai
Published: March 2019

A novel method of the synthesis of tertiary aromatic amides from tertiary benzylamines with high atom utilization has been developed. The reaction undergoes a different mechanism, which is divided into two parts: firstly tertiary amine is decomposed (into benzaldehyde and secondary amine) via TBAI/TBHP–mediated C−N bond cleavage, then tertiary amide is generated through the oxidative amidation of the intermediates products (benzaldehyde and secondary amine). These two parts of reaction are integrated into a single operation, which provides moderate to excellent yields with a wide suabstrate scope.
Regioselective Synthesis, Molecular Descriptors of (1,5‐Disubstituted 1,2,3‐Triazolyl)Coumarin/Quinolone Derivatives and Their Docking Studies against Cancer Targets
Authors: Ansary Inul , Roy Hiren , Das Arijit , Mitra Debanjan , Bandyopadhyay Amal Kumar
Published: March 2019

A series of (1,5‐disubstituted 1,2,3‐triazolyl)coumarin/quinolone derivatives (tcd and tqd) have been synthesized in good to excellent yields via Ag2O NPs catalyzed azide‐alkyne cycloaddition reactions. We then tested the drug‐likeness of tcd and tqd by analyzing molecular descriptors. Rational drug design showed that these derivatives indeed are potential anticancer agents against tankyrases.
Synthesis, Hydrolysis, Reduction and Nitrolysis of Glycoluril‐Derived Precursors: Another Attempt toward the Synthesis of Nitramine Explosives
Authors: Liu Wenjin , Xu Zhibin , Wang Rui , Zhang Chenfan , Yan Qiaoli , Meng Zihui
Published: March 2019

A new glycoluril derivative‐1H, 4H, 5H, 8H‐2, 3a, 4a, 6, 7a, 8a‐hexaazacyclopenta[def]fluorene‐4, 8‐dione, hexahydro‐2, 6‐bis(phenylmethyl) (3) is strategically designed and synthesized through the reaction between glycoluril, formaldehyde and benzylamine with the optimized molar ratio of 1:6:2. Compound 3 is fully characterized by 1H NMR, 13C NMR, IR, MS and X‐ray single crystal diffraction. Reduction of compound 3 delivers a potential precursor‐imidazo[4, 5‐d]imidazole, octahydro‐hexahydro‐2, 6‐bis(phenylmethyl) (4) for the synthesis of novel nitramine explosives (i.e. bicyclo‐HMX and bi‐RDX). The nitration and hydrolysis of compound 4 are investigated in detail and three ring‐opened molecules N, 2, 4‐trinitro‐benzenemethanamine (8a), N, 2‐dinitro‐benzenemethanamine (8b) and N‐methylene‐benzenemethanamine (9) are obtained.
Degradation of 4‐chlorophenol by BM Fe/Cu‐O2 system: The symbiosis of and ·OH radicals
Authors: Fan Jinhong , Qin Hehe , Zhang Yunfei , Jiang Simin
Published: March 2019

In this study, Fe/Cu bimetal composite was prepared by high‐energy ball milling (BM) method for the removal of refractory organics. The BM Fe/Cu bimetal was characterized by SEM‐EDS, XRD, and XPS. Evenly distributed Fe and Cu was observed in the EDS mapping. In contrasting experiments, the removal rate of 4‐chlorophenol (4‐CP) by BM Fe/Cu materials was about 10‐fold faster than that by chemical substitution deposition (CSD) of Fe/Cu material. Complete 4‐CP removal and 66.7% of total organic carbon (TOC) mineralization in the BM Fe/Cu–O2 system were achieved. Dissolved oxygen plays a crucial role for 4‐CP degradation through the in situ generation of reactive oxygen species (ROS) such as H2O2, ·OH, and via oxygen activation reactions. The predominant reactive radicals were identified to be and ·OH through ESR technique and inhibition experiments. The coexistence of oxidation and reduction of 4‐CP in the BM Fe/Cu‐O2 system was proposed.

Practitioner points

4‐CP removal rate by BM Fe/Cu is 10‐fold faster than that by CSD Fe/Cu at the same conditions.

Complete 4‐CP removal and 66.7% of TOC reduction were achieved.

All three ROS including ·OH, , and H2O2 coexisted in the BM Fe/Cu‐O2 system.

A harmonious coexistence of oxidation and reduction mechanism was proposed.
Two-year follow-up of the OptiTrain randomised controlled exercise trial
Authors: Bolam Kate A. , Mijwel Sara , Rundqvist Helene , Wengström Yvonne
Published: March 2019

Purpose

The aim of this study was to determine if there were any differences in health-related outcomes and physical activity (PA) between the two OptiTrain exercise groups and usual care (UC), 2 years post-baseline.

Methods

The OptiTrain study was a three-arm randomised controlled trial comparing 16 weeks of concurrent aerobic high-intensity interval training (HIIT) and progressive resistance exercise (RT-HIIT) or concurrent HIIT and continuous moderate-intensity aerobic exercise (AT-HIIT) to UC in 206 patients with breast cancer undergoing chemotherapy. Eligible participants were approached 2 years following baseline to assess cancer-related fatigue, quality of life, symptoms, muscle strength, cardiorespiratory fitness, body mass, PA, sedentary behaviour, and sick leave.

Results

The RT-HIIT group reported lower total cancer-related fatigue, (− 1.37, 95% CI − 2.70, − 0.04, ES = − 0.06) and cognitive cancer-related fatigue (− 1.47, 95% CI − 2.75, − 0.18, ES = − 0.28), and had higher lower limb muscle strength (12.09, 95% CI 3.77, 20.40, ES = 0.52) than UC at 2 years. The AT-HIIT group reported lower total symptoms (− 0.23, 95% CI − 0.42, − 0.03, ES = − 0.15), symptom burden (− 0.30, 95% CI − 0.60, − 0.01, ES = − 0.19), and body mass − 2.15 (− 3.71, − 0.60, ES = − 0.28) than UC at 2 years.

Conclusion

At 2 years, the exercise groups were generally experiencing positive differences in cancer-related fatigue (RT-HIIT), symptoms (AT-HIIT), and muscle strength (RT-HIIT) to UC. The findings provide novel evidence that being involved in an exercise program during chemotherapy can have long-term benefits for women with breast cancer, but that strategies are needed to create better pathways to support patients to maintain physical activity levels.

Trial registration

Clinicaltrials.gov registration number: NCT02522260. Trial registered on 9 June 2015. https://clinicaltrials.gov/ct2/show/NCT02522260. Retrospectively registered.
Revised approach for the prediction of functional size of mobile application
Authors: Mushtaq Ziema , Wahid Abdul
Published: March 2019

Mobile applications affect our everyday activities and have become more and more information centric. Effort estimation for mobile application is an essential factor to consider in the development cycle. Due to feature complexities and size, effort estimation of mobile applications poses a continued challenge for developers. This paper attempts to adapt COSMIC Function Point and Unified Modeling Language (UML) techniques to estimate the size of a given mobile application. The COSMIC concepts capture data movements of the functional processes whereas the UML class analyzes them. We utilize the Use Case Diagrams, sequence diagrams and class diagrams for mapping the Function user requirements for sizing mobile applications. We further present a new size measurement technique; Unadjusted Mobile COSMIC Function points (UMCFP) to get the functional size of mobile application using Mobile Complex Factors as an input. In this study eight mobile applications were analyzed using UMCFP, Function Point Analysis and COSMIC Function Point. The results were compared with the actual size of previous Mobile application projects.
3279 First in Man
Authors: Adang Laura , Gavazzi Francesco , Giorgis Valentina De , Simone Micaela De , Fazzi Elisa , Galli Jessica , Koh Jamie , Kramer-Golinkoff Julia , Orcesi Simona , Peer Kyle , Ulrick Nicole
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: A mimic of congenital infections and a rare genetic cause of interferon overproduction, Aicardi Goutières Syndrome (AGS) results in significant neurologic disability. AGS is caused by pathogenic changes in the intracellular nucleic acid sensing machinery (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1). All affected individuals exhibit neurologic impairment: from mild spastic paraparesis to severe tetraparesis and global developmental delay. We hypothesize that genotype influences the heterogeneous developmental trajectory found in AGS. METHODS/STUDY POPULATION: To characterize this spectrum, age and symptoms at presentation and longitudinal developmental skill acquisition was collected from an international cohort of children (n=88) with genetically confirmed AGS. RESULTS/ANTICIPATED RESULTS: We found that individuals present at variable ages, with the largest range in SAMHD1, ADAR, and IFIH1. There are 3 clusters of symptoms at presentation: altered mental status (irritability or lethargy), systemic inflammatory symptoms, and acute neurologic symptoms, with variability across all genotypes. By creating Kaplan-Meier curves for developmental milestones, we were able to create genotype-based developmental trajectories for the children affected by the 5 most common genotypes: TREX1, IFIH1, SAMHD1, ADAR, and RNASEH2B. Individuals with AGS secondary to TREX1 were the most severely affected, significantly less likely to reach milestones compared to the other genotypes, including head control, sitting, and nonspecific mama/dada (p-value <0.005). Individuals affected by SAMHD1, IFIH1, and ADAR collectively attained the most advanced milestones, with 44% of the population achieving a minimum of a single word and 31% able to walk independently. Three retrospective scales were also applied: Gross Motor Function Classification System, Manual Ability Classification Scale, and Communication Function Classification System. Within each genotypic cohort, there was pronounced heterogeneity. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results demonstrate the influence of genotype on early development, but also suggest the importance of other unidentified variables. These results underscore the need for deep phenotyping to better characterize subcohorts within the AGS population.
3526 Healthy eating, physical activity, sleep and cognitive function in elderly population: Data from National Health and Nutrition Examination Survey 2011-2014
Authors: Shaheen Magda
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: To examine the relationship between healthy eating, physical activity (PA), sleep problem and hours of sleep and cognitive function among elderly population and the racial/ethnic differences in this relation. METHODS/STUDY POPULATION: We analyzed data from National Health and Nutrition Examination Survey 2014-2016 for 882 population 60 years and older. Cognitive status was measured by the Digit Symbol Substitution (DSS) exercise score and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) total score. Healthy eating index (HEI), PA, and sleep problem and hours of sleep were assessed by questionnaire. The association between cognitive function and HEI, PA, sleep problem and hours of sleep were assessed by linear regression after adjusting for age, gender, race/ethnicity, poverty level, lipid profile, fasting glucose level, alcohol, body mass index, stroke and education. Data were analyzed using Stata 14 considering design and sample weight and p<0.05 is statistically significant. RESULTS/ANTICIPATED RESULTS: CERAD total score was associated with HEI (Adjusted B = 0.07, 95% Confidence Interval (CI) = 0.01-0.13, p = 0.02) and not associated with physical activity or sleep problem or hours of sleep (p > 0.05). Animal fluency score was associated only with HEI (Adjusted B = 0.05, 95% CI = 0.01-0.09, p = 0.02). DDS score was not associated with HEI, PA, or sleep problem (p > 0.05) but associated with hours of sleep (p = 0.03). Stratified analysis by race/ethnicity showed that CERAD total score was associated with HEI only in White (Adjusted B = 0.08, 95% CI = 0.01-0.15, p = 0.02). DISCUSSION/SIGNIFICANCE OF IMPACT: CERAD total score was associated with HEI and not associated with PA or sleep problem. Promoting healthy eating is important for improving cognition in elderly population. Culturally sensitive and linguistically appropriate programs that involve community and care providers are needed to promote healthy eating for elderly population.
3449 Bacterial biotransformation of chemotherapeutics may promote diversity among the intestinal microbiota
Authors: Blaustein Ryan Andrew , Seed Patrick Casey , Hartmann Erica Marie
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: This study aims to test the hypothesis that bacterial biotransformation of chemotherapeutics promotes gut microbial diversity by enhancing persistence of drug-sensitive taxa. METHODS/STUDY POPULATION: The impacts of doxorubicin on a model community of gut bacteria was investigated in vitro in anaerobic batch culture. The synthetic community was composed of specific members predicted by genomic analysis to be sensitive to the therapeutic (i.e., Clostridium innocuum, Lactobacillus sp.), resistant via putative biotransformation (i.e., Escherichia coli, Klebsiella pneumoniae), or resistant via putative efflux (i.e., Enterococcus faecalis). Bacterial growth was monitored in monocultures by measuring OD600 and standard plate counts, and in mixed cultures by strain-targeted qPCR. Doxorubicin concentration was detected via absorbance assay. RESULTS/ANTICIPATED RESULTS: Strains with predicted resistance to doxorubicin by drug biotransformation significantly lowered concentrations of the drug in culture media. In contrast, E. faecalis proved resistant without evidence of drug transformation. Predicted sensitive strains were growth-repressed by the doxorubicin, but able to grow in spent media where biotransformation had occurred. However, they remained growth-repressed in spent media from E. faecalis where drug transformation had not been observed. Bacterial growth kinetics in mixed batch culture were dependent on starting bacterial concentrations and timing of drug exposure. DISCUSSION/SIGNIFICANCE OF IMPACT: This work will be extended to model microbial community responses to doxorubicin as a factor of microbial interactions and extent of drug transformation prior its exposure to sensitive strains. The resulting model will have translational implications for mitigating health risks during pediatric cancer treatment.
3071 Cell Survival in Corneal Endothelial Dystrophies
Authors: Shyam Rajalekshmy , Ogando Diego , Choi Moonjung , Bonanno Joseph
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Purpose - The goal of this study is to understand how loss of the membrane protein SLC4A11 alters endothelial cell metabolism thereby producing Corneal Endothelial Dystrophy. Studies from our lab indicated that glutamine-dependent mitochondrial dysfunction is one of the outcomes of SLC4a11 loss. In the current study, we ask if autophagy and mitophagy pathways and the signaling pathways that regulate these processes are altered in SLC4a11 KO cells. METHODS/STUDY POPULATION: Methods – Immortalized mouse WT and SLC4a11 KO cell lines were incubated in DMEM with and without 0.5mM glutamine for 6 hours. In order to assess mitophagy, cells were stained using Lysotracker Red and Mitotracker Green. Colocalization co-efficients of red and green channels were obtained for at least 35 cells using Zeiss-Zen Pro software. Student’s t-test was used to determine statistical significance. For Western Blots, antibodies against LC3b, AMPK, pAMPK, and b-actin were used to examine autophagy flux and potential signaling pathways that regulate autophagy. RESULTS/ANTICIPATED RESULTS: Results – In the presence of glutamine, the colocalization co-efficient of Lysotracker Red and Mitotracker Green channels was significantly increased in KO cells (0.74 ±0.18) relative to WT (0.58±0.20) with a p-value ≤0.0024. In the absence of glutamine, the colocalization co-efficient was reversed, for KO cells 0.54 ±0.14 and for WT cells 0.77±0.0.16 with a p-value ≤0.0001, suggesting increased mitophagy by glutamine in KO cells. Western Blots indicated that glutamine increased autophagy flux, as indicated by increased levels of LC3b following bafilomycin A treatment in KO cells. Concomitantly, there was an increase in pAMPK/AMPK levels suggesting a potential mechanism for increased mitophagy. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusion and Future studies –Our data indicates enhanced mitophagy as well as autophagy in SLC4a11 KO cells. Future studies will determine whether these processes regulate cell survival in mouse models of corneal endothelial dystrophies.
3157 Relationship between abnormal nocturnal blood pressure patterns and end-organ damage following heart transplantation.
Authors: Oreschak Kris , Wolfel Eugene E. , Ambardekar Amrut V. , Aquilante Christina L.
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Heart transplant (HTx) recipients are more likely to exhibit abnormal circadian blood pressure (BP) patterns (e.g., lack of nocturnal dip in BP) compared with the general population. Our goal was to assess the relationship between abnormal circadian BP patterns and end-organ damage in HTx recipients. METHODS/STUDY POPULATION: The retrospective study included 30 patients who were ≥ 6 months post-heart transplant and had 24-hour ambulatory BP data collected during a parent study. Nocturnal BP decline was categorized as: ≥10% decline, dipper; <10% decline, non-dipper. The primary end-organ damage outcomes we plan to analyze are left ventricular hypertrophy (LVH), chronic kidney disease (CKD), and proteinuria. The association between nocturnal BP decline and the primary outcomes will be analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: The study cohort consists of 83% men and 83% Caucasians (mean age=57±14 years; mean time post-transplant =9.0±6.6 years). Systolic and diastolic non-dippers represent 53.3% and 40% of the cohort, respectively. Data are currently being analyzed for the association between nocturnal BP dipping status and LVH, CKD, and proteinuria. These findings will be presented at the conference. DISCUSSION/SIGNIFICANCE OF IMPACT: An understanding of factors, such as abnormal circadian BP patterns, that contribute to the development of end-organ damage following HTx may provide opportunities to improve BP management and prevent adverse complications in this high-risk population.
3086 Virtual World-based Cardiac Rehabilitation to Promote Healthy Lifestyle Among Cardiac Patients
Authors: Brewer LaPrincess , Kaihoi Brian , Leth Shawn , Squires Ray , Thomas Randal , Scales Robert , Trejo-Gutierrez Jorge , Kopecky Stephen
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: Our aim was to assess the feasibility and acceptability of a VW-based cardiac rehabilitation (CR) program (Destination Rehab) as an extension of a face-to-face conventional CR program. We hypothesized that a VW-based CR program could be successfully implemented as an extension of conventional CR and would have high acceptability among cardiac patients. METHODS/STUDY POPULATION: We recruited 30 adult cardiac patients (10/site) hospitalized at Mayo Clinic Hospitals in Rochester, MN, Jacksonville, FL or Scottsdale, AZ with a diagnosis for CR (eg, acute coronary syndrome (ACS), heart failure, elective percutaneous coronary intervention (PCI)). Other inclusion criteria included at least 1 modifiable, lifestyle risk factor target: sedentary lifestyle (< 3 hours physical activity (PA)/week), unhealthy diet (< 5 servings fruits and vegetables/day) or current smoking (>1 year). Patients participated in an 8-week, health education program using a VW platform from a prior proof-of-concept study and provided intervention usability, usefulness and satisfaction feedback. We assessed cardiovascular (CV) health behaviors (diet, PA) and risk factors (eg, blood pressure (BP), lipids) at baseline and immediate post-intervention. RESULTS/ANTICIPATED RESULTS: Among 30 patients enrolled (mean age; 59 years; 50% women; 65% <college graduate; 32% annual household income <$50,000), 28 (98%) completed the study. The majority (64%) were enrolled in conventional CR with a high session completion rate (median 36 sessions, interquartile range 8-36). The most common CR indication was PCI (68%). There were statistically significant improvements in PA from baseline to post-intervention: vigorous PA, +10.7 (SD 11.7) minutes/day (p = 0.05) and flexibility exercises +0.9 (SD 0.9) days/week for men (p=0.05). There were favorable trends in risk factors: systolic BP (−6.8 mmHg, SD 29.8), total cholesterol (−31.6 mg/dL, SD 46.2) and LDL (−26 mg/dL, SD 44.8) from baseline to post-intervention, although not statistically significant. The majority reported that they would continue to use VW as a resource (76%) and agreed/strongly agreed that the program improved their heart health knowledge (86%) and assisted with adapting healthier lifestyle (100%). Overall, the VW CR program received a rating of 8 (scale 0-10). DISCUSSION/SIGNIFICANCE OF IMPACT: VW-based CR program is a feasible, highly acceptable and innovative platform to influence health behaviors and CV risk and can increase accessibility to disadvantaged populations with higher CVD burdens.
3561 Creating a Scientific Community for Outcomes Researchers
Authors: Reamey Rebecca Avery , Mugavero Michael J
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: 1. Foster a community of scholars – by centering on training and professional development programs that assist with career progression. 2. Improve heath equity for the community – by developing innovative ways to capture data, address problems, deliver solutions, and disseminate results to patients and people everywhere. 3. Facilitate interdisciplinary teams at all career stages – by providing opportunities for researchers, regardless of discipline and career stage, to engage in dialogue with others. SCOR has developed a series of programs to address each stage in the career arch. LEAD: Learn Enhance Advance Drive develops a pipeline of future leaders within UAB by engaging junior faculty and staff who are in leadership roles or will be in leadership roles soon to develop fundamental competencies. The one-year, cohort-based program enables junior faculty and staff to enhance their interpersonal skills, professional skills, and leadership skills. The program uses the Leadership Competency Model to provide the framework for the chosen topics. The K2R program provides structured activities over a 4– 5 month timeline to assist cohorts of scholars in their preparation of a specific grant application. Leveraging existing programs, like Project Panels, and offerings including a Specific Aims Workshop, K and R Writing Groups, and Mock Study Section, the SCOR extends the engagement of scholars in their ongoing research development. METHODS/STUDY POPULATION: Using quantitative methods, we have conducted surveys to measure effectiveness of weekly didactic sessions and topics. We use qualitative methods such as interviews and focus groups to better understand the relevance of the individual programs and the larger community of SCOR. RESULTS/ANTICIPATED RESULTS: N/A DISCUSSION/SIGNIFICANCE OF IMPACT: Creating a community of interdisciplinary investigators will greatly impact research at the institution.
3040 How to write your first scholarly journal article using reporting guidelines as a template
Authors: Selfe Terry Kit
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: The objective of this session is to support and encourage novice, unpublished researchers to turn their poster content into a manuscript publishable in a scholarly journal, by showing them concrete steps to follow and research study reporting standards to use as a template. METHODS/STUDY POPULATION: We will cover the following topics: choosing a journal, finding the journal’s requirements, locating the reporting standard for the study type (e.g., CONSORT for randomized trials), and structuring the manuscript appropriately per International Committee of Medical Journal Editors (ICMJE) recommendations (e.g., Introduction, Methods, Results, and Discussion). RESULTS/ANTICIPATED RESULTS: It is anticipated that by the end of the session, attendees should be able to: Select an appropriate journal; Organize a manuscript according to ICMJE guidelines; Compose a manuscript based on the applicable reporting standard (e.g. CONSORT). DISCUSSION/SIGNIFICANCE OF IMPACT: Providing novice researchers with information and resources that demystify the process of writing a manuscript suitable for a scholarly journal, is expected to bolster their confidence and increase the likelihood they will create and submit publishable manuscripts; thereby improving the dissemination of research findings and increasing research impact.
3189 Transmitting wisdom and enhancing KL2 training through the use of exit presentations
Authors: Lamere Michelle , Larson Megan , Ingbar David H. , Lim Kelvin O.
Published: March 2019

OBJECTIVES/SPECIFIC AIMS: -Transmit learning and wisdom from past scholars -Predispose new scholars towards a receptive attitude -Normalize struggle and failure on the road to success -Encourage a community of accomplishment and celebration -Connect the scholar METHODS/STUDY POPULATION: The exit presentations were given by NCATS funded junior faculty in the CTSI KL2 Scholars Program who had graduated. All KL2 Scholars take part in the K Scholar Multidisciplinary Seminar Series that meets weekly during the academic calendar. The departed scholars returned for the presentations the following semester. The audience was made up of KL2 who had started with a later cohort, the CTSI KL2 program is a 3-year program, and newly appointed scholars. Scholars were given 12-15 minutes to cover: 1) What was learned, 2) Accomplishments on specific aims, 3) Next steps for project and career, and 4) Recommendations for other scholars. Presentations were collected and reviewed for recurring themes. Themes were grouped and quotes were included to identify nuance. RESULTS/ANTICIPATED RESULTS: From the 17 exit presentations, six themes were identified: 1) Don’t miss the forest for the trees (x10) – “the KL2 program helps to fill in gaps scholars don’t realize they have – it is about more than just the research project, trust in the process and let the program help keep you on track.” 2) Diversify and keep an open mind (x7) – “focus is important but diversifying research and reorganizing priorities is ok.” 3) Don’t be discouraged by failure (x6) –” perseverance is key, all success comes on the heels of many failures.” 4) Importance of building network inside and outside of Scholar program (x6) – “importance of exploring and establishing collaborations” 5) Learn to say no and yes (x5) – “protect your time but be open to opportunities” 6) Seek advice and criticism but don’t follow blindly (x4) DISCUSSION/SIGNIFICANCE OF IMPACT: The use of exit presentations for graduating KL2 Scholars is a useful tool in transmitting wisdom and enhancing subsequent KL2 cohorts. The Scholar’s experience and trajectory, share personal insights and recommendations to help other Scholars get the most out of their KL2 experience, give the community a chance to celebrate the Scholar’s accomplishments, and provide the Scholar with a sense of closure in their KL2 journey. Within the exit presentations, six common themes emerged relating to best practices on making good use of resources and guidance, and learning to interact and navigate within networks and responsibilities in a mature way. Scholars in the audience benefit from hearing the insights and advice from their predecessors. The identification of themes helps the program to understand where it adds value.