bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Targeting of TFE3/IRS-1/PI3K/mTOR Axis in Translocation Renal Cell Carcinoma
Authors: Damayanti Nur P. , Budka Justin A. , Khella Heba W.Z , Ferris Mary W. , Ku Sheng Yu , Kauffman Eric , Wood Anthony C. , Ahmed Khunsha , Chintala Venkata Nithinsai , Adelaiye-Ogala Remi , Elbanna May , Orillion Ashley , Chintala Sreenivasulu , Kao Chinghai , Linehan W. Marston , Yousef George M. , Hollenhorst Peter C. , Pili Roberto 
Published: July 2018

Abstract

Purpose:
Translocation renal cell carcinoma (tRCC) represents a rare subtype of kidney cancer associated with various TFE3, TFEB, or MITF gene fusions that are not responsive to standard treatments for RCC. Therefore, the identification of new therapeutic targets represents an unmet need for this disease.

Experimental Design:
We have established and characterized a tRCC patient-derived xenograft, RP-R07, as a novel preclinical model for drug development by using next-generation sequencing and bioinformatics analysis. We then assessed the therapeutic potential of inhibiting the identified pathway using in vitro and in vivo models.

Results:
The presence of a SFPQ-TFE3 fusion [t(X;1) (p11.2; p34)] with chromosomal break-points was identified by RNA-seq and validated by RT-PCR. TFE3 chromatin immunoprecipitation followed by deep sequencing analysis indicated a strong enrichment for the PI3K/AKT/mTOR pathway. Consistently, miRNA microarray analysis also identified PI3K/AKT/mTOR as a highly enriched pathway in RP-R07. Upregulation of PI3/AKT/mTOR pathway in additional TFE3–tRCC models was confirmed by significantly higher expression of phospho-S6 (P &lt; 0.0001) and phospho-4EBP1 (P &lt; 0.0001) in established tRCC cell lines compared with clear cell RCC cells. Simultaneous vertical targeting of both PI3K/AKT and mTOR axis provided a greater antiproliferative effect both in vitro (P &lt; 0.0001) and in vivo (P &lt; 0.01) compared with single-node inhibition. Knockdown of TFE3 in RP-R07 resulted in decreased expression of IRS-1 and inhibited cell proliferation.

Conclusions:
These results identify TFE3/IRS-1/PI3K/AKT/mTOR as a potential dysregulated pathway in TFE3–tRCC, and suggest a therapeutic potential of vertical inhibition of this axis by using a dual PI3K/mTOR inhibitor for patients with TFE3–tRCC.
Using “Local Climate Zones” to Detect Urban Heat Island on Two Small Cities in Alabama
Authors: Chieppa Jeff , Bush Austin , Mitra Chandana 
Published: July 2018

AbstractClassifying “urban” and “rural” environments is a challenge in understanding urban climate, specifically urban heat islands (UHIs). Stewart and Oke developed the “local climate zone” (LCZ) classification system to clarify these distinctions using 17 unique groups. This system has been applied to many areas around the world, but few studies have attempted to utilize them to detect UHI effects in smaller cities. Our aim was to use the LCZ classification system 1) to detect UHI in two small cities in Alabama and 2) to determine whether similar zones experienced similar intensity or magnitude of UHIs. For 1 week, we monitored hourly temperature in two cities, in four zones: compact low-rise, open low-rise, dense forests, and water. We found that urban zones were often warmer for overall, daytime, and nighttime temperatures relative to rural zones (from −0.1° to 2.8°C). In addition, we found that temperatures between cities in similar zones were not very similar, indicating that the LCZ system does not predict UHI intensity equally in places with similar background climates. We found that the LCZ classification system was easy to use, and we recognize its potential as a tool for urban ecologists and urban planners.
Prediction of postoperative lung function in lung cancer patients using perfusion scintigraphy
Authors: Yoo Ik Dong , Im Jooyeon Jamie , Chung Yong-An , Choi Eun Kyung , Oh Jin Kyung , Lee Sang-Hoon 
Published: July 2018

Background Predicting postoperative lung function is critical in lung cancer patients. Perfusion scintigraphy has been used to estimate postoperative function after lung resection. Purpose To evaluate the usefulness of the posterior oblique method in relation to other conventional processing methods for predicting postoperative lung function using lung perfusion scintigraphy. Material and Methods Fifty-five patients with non-small-cell lung cancer who underwent lobectomy were enrolled. Forced expiratory volume in 1 s (FEV1) values were obtained from preoperative and postoperative pulmonary function tests. After performing lung perfusion scintigraphy, predicted FEV1 values were calculated using the segment, conventional, posterior, and posterior oblique methods. Postoperative FEV1 values were compared with predicted FEV1 values. Results The mean value of the preoperative FEV1 was 2.29 L and that of the postoperative FEV1 was 1.89 L. The mean values of the predicted postoperative FEV1 values for the segment, conventional, posterior, and posterior oblique were 1.83 L, 1.94 L, 1.88 L, and 1.89 L, respectively. Between the observed and predicted FEV1 values, there was a strong correlation without significant difference except for conventional method. Bland–Altman analysis showed that segment and posterior methods underestimated the FEV1, whereas conventional and posterior oblique methods overestimated the FEV1. Conclusion Predictions with each processing method of lung perfusion scintigraphy showed nearly similar results to the actual postoperative lung function. The posterior oblique method of lung perfusion scintigraphy showed a very small difference to such an extent as to be equal to the observed FEV1, implying that this method may be applied for predicting postoperative lung function in lung cancer patients.
Decreased apolipoprotein A4 and increased complement component 3 as potential markers for papillary thyroid carcinoma: A proteomic study
Authors: Farrokhi Yekta Reyhaneh , Arefi Oskouie Afsaneh , Rezaei Tavirani Mostafa , Mohajeri-Tehrani Mohammad R. , Soroush Ahmad R. 
Published: July 2018

Background: Thyroid carcinomas have comprised the fastest rising incidence of cancer in the past decade. Currently, the diagnosis of thyroid tumors is performed by the fine-needle aspiration biopsy (FNAB) method, which still holds some challenges and limitations, mostly in discriminating malignant and benign lesions. Therefore, the development of molecular markers to distinguish between these lesion types are in progress. Methods: A 2D-PAGE separation of proteins was performed followed by tandem mass spectrometry with the aim of discovering potential serum protein markers for papillary thyroid carcinoma and multinodular goiter. Protein–protein interaction network analysis revealed the most important pathways involved in the progression of papillary thyroid cancer. The enzyme-linked immunosorbent assay method was used to confirm a part of the results. Results: The significantly altered proteins included C3, C4A, GC, HP, TTR, APOA4, APOH, ORM2, KRT10, AHSG, IGKV3-20, and IGKC. We also confirmed that increased complement component 3 and decreased apolipoprotein A4 occurred in papillary thyroid cancer. Network investigations demonstrated that complement activation cascades and PPAR signaling might play a role in the pathogenesis of thyroid cancer. Conclusion: The results demonstrated that serum proteomics could serve as a viable method for proposing novel potential markers for thyroid tumors. Surely, further research must be performed in larger cohorts to validate the results.
Preclinical and phase I clinical studies of KW-2450, a dual IGF-1R/IR tyrosine kinase inhibitor, in combination with lapatinib and letrozole
Authors: Umehara Hiroshi , Maekawa Yoshimi , Koizumi Fumito , Shimizu Makiko , Ota Toshio , Fouad Tamer M. , Willey Jie , Kaito Hidekuni , Shiraishi Norihiko , Nakashima Daisuke , Akinaga Shiro , Ueno Naoto T. 
Published: July 2018

Background: KW-2450 is an oral dual insulin-like growth factor-1 receptor/insulin receptor tyrosine kinase inhibitor. We investigated the in vitro and in vivo preclinical activity of KW-2450 plus lapatinib and letrozole and conducted a phase I trial of the triple-drug combination in one male and 10 postmenopausal female patients with advanced/metastatic hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Methods: A series of in vitro and in vivo animal studies was undertaken of KW-2450 in combination with lapatinib and hormonal agents. The phase I trial was conducted to establish the safety, tolerability, and recommended phase II dose (RP2D) of KW-2450 administered in combination with lapatinib and letrozole. Results: Preclinical studies showed KW-2450 and lapatinib act synergistically to induce in vitro apoptosis and inhibit growth of HER2-positive MDA-MB-361 and BT-474 breast cancer cell lines. This combined effect was confirmed in vivo using the MDA-MB-361 xenograft model. KW-2450 showed synergistic in vitro growth inhibition with letrozole and 4-hydroxytamoxifen in ER-positive MCF-7 breast cancer cells and MCF-7-Ac1 aromatase-transfected MCF-7 cells. In the phase I study, dose-limiting toxicity (DLT; grade 3 rash and grade 3 hyperglycemia, respectively) occurred in two of three patients at the dose of KW-2450 25 mg/day plus lapatinib 1500 mg/day and letrozole 2.5 mg/day. The RP2D of the triple-drug combination was established as KW-2450 25 mg/day, lapatinib 1250 mg/day, and letrozole 2.5 mg/day with no DLT at this dose level. Conclusions: The proposed phase II study of the RP2D for the triple-drug combination did not progress because of anticipated difficulty in patient enrollment and further clinical development of KW-2450 was terminated.
Comparison between effect of desflurane/remifentanil and propofol/remifentanil anesthesia on somatosensory evoked potential monitoring during scoliosis surgery—A randomized controlled trial
Authors: Hasan M Shahnaz , Tan Jin-Keat , Chan Chris Yin Wei , Kwan Mun Keong , Karim Fathil Syafiq Abdul , Goh Khean-Jin 
Published: July 2018

Background: Drugs used in anesthesia can affect somatosensory evoked potential (SSEP) monitoring, which is used routinely for intraoperative monitoring of spinal cord integrity during spinal surgery. Objective: The objective of this study was to determine whether combined total intravenous anesthesia (TIVA) technique with propofol/remifentanil is associated with less SSEP suppression when compared to combined volatile agent desflurane/remifentanil anesthesia during corrective scoliosis surgery at a comparable depth of anesthesia. Design: It is a randomized controlled trial. Setting: The study was conducted at the Single tertiary University Hospital during October 2014 to June 2015. Patients: Patients who required SSEP and had no neurological deficits, and were of American Society of Anesthesiologist I and II physical status, were included. Patients who had sensory or motor deficits preoperatively and significant cardiovascular and respiratory disease were excluded. A total of 72 patients were screened, and 67 patients were randomized and allocated to two groups: 34 in desflurane/remifentanil group and 33 in TIVA group. Four patients from desflurane/remifentanil group and three from TIVA group were withdrawn due to decrease in SSEP amplitude to <0.3 µV after induction of anesthesia. Thirty patients from each group were analyzed. Interventions: Sixty-seven patients were randomized to receive TIVA or desflurane/remifentanil anesthesia. Main outcome measures: The measurements taken were the amplitude and latency of SSEP monitoring at five different time points during surgery: before and after the induction of anesthesia, at skin incision, at pedicle screw insertion, and at rod insertion. Results: Both anesthesia techniques, TIVA and desflurane/remifentanil, resulted in decreased amplitude and increased latencies of both cervical and cortical peaks. The desflurane/remifentanil group had a significantly greater reduction in the amplitude ( p = 0.004) and an increase in latency ( p = 0.002) of P40 compared with the TIVA group. However, there were no differences in both amplitude ( p = 0.214) and latency ( p = 0.16) in cervical SSEP between the two groups. Conclusions: Compared with TIVA technique, desflurane/remifentanil anesthesia caused more suppression in cortical SSEP, but not in cervical SSEP, at a comparable depth of anesthesia.
Application of scanning electron diffraction in the transmission electron microscope for the characterisation of dislocations in minerals
Authors: Nzogang Billy C. , Mussi Alexandre , Cordier Patrick 
Published: July 2018

AbstractWe present an application of scanning electron diffraction for the characterisation of crystal defects in olivine, quartz and phase A (a high pressure hydrated phase). In this mode, which takes advantage of the ASTAR™ module from NanoMEGAS, a slightly convergent probe is scanned over the sample with a short acquisition time (a few tens of ms) and the spot patterns are acquired and stored for further post-processing. Originally, orientation maps were constructed from automatic indexing at each probe location. Here we present another application where images are reconstructed from the intensity of diffraction spots, producing either so-called ‘virtual’ bright- or dark-field images. We show that these images present all the characteristics of contrast (perfect crystal or defects) of conventional transmission electron microscopy images. Data are acquired with a very short time per probe location (a few tens of milliseconds), this technique appears very attractive for the characterisation of beam-sensitive materials. However, as the acquisition is done at a given orientation, fine tuning of the diffraction conditions at a given location for each reflection is not possible. This might present a difficulty for some precise, quantitative contrast analysis.
Patients with depression who self-refer for transcranial magnetic stimulation treatment: exploratory qualitative study
Authors: Clarke Martin , Lankappa Sudheer , Burnett Mark , Khalifa Najat , Beer Charlotte 
Published: July 2018

Aims and methodAs part of a larger clinical trial concerning the use of transcranial magnetic stimulation (TMS) for treatment-resistant depression, the current study aimed to examine referral emails to describe the clinical characteristics of people who self-refer and explore the reasons for self-referral for TMS treatment. We used content analysis to explore these characteristics and thematic analysis to explore the reasons for self-referral.ResultsOf the 98 referrals, 57 (58%) were for women. Depressive disorder was the most commonly cited diagnosis, followed by bipolar affective disorder. Six themes emerged from the thematic analysis: treatment resistance, side-effects of other treatments, desperation for relief, proactively seeking information, long-term illness and illness getting worse.Clinical implicationsTMS has recently been recommended in the UK for routine use in clinical practice. Therefore, the number of people who self-refer for TMS treatment is likely to increase as its availability increases.Declaration of interestNone.
Postoperative Hypotension and Surgical Site Infections After Colorectal Surgery: A Retrospective Cohort Study
Authors: Yilmaz Huseyin O. , Babazade Rovnat , Leung Steve , Zimmerman Nicole M. , Makarova Natalya , Saasouh Wael , Stocchi Luca , Gorgun Emre , Sessler Daniel I. , Turan Alparslan 
Published: July 2018

BACKGROUND:
Hypotension compromises local tissue perfusion, thereby reducing tissue oxygenation. Hypotension might thus be expected to promote infection. Hypotension on surgical wards, while usually less severe than intraoperative hypotension, is common and often prolonged. In this retrospective cohort study, we tested the hypotheses that there is an association between surgical site infections and low postoperative time-weighted average mean arterial pressure and/or postoperative minimum mean arterial pressure.

METHODS:
We considered patients who had colorectal surgery lasting ≥1 hour at the Cleveland Clinic between 2009 and 2013. We defined blood pressure exposures as time-weighted average (primary) and minimum mean arterial pressure (secondary) within 72 hours after surgery. We assessed associations between continuous blood pressure exposures with a composite of deep and superficial surgical site infection using separate severity-weighted average relative effect generalized estimating equations models, each using an unstructured correlation structure and adjusting for potentially confounding variables.

RESULTS:
A total of 5896 patients were eligible for analysis. Time-weighted mean arterial pressure and surgical site infection were not significantly associated, with an estimated odds ratio (95% CI) of 1.03 (0.99–1.08) for a 5-mm Hg decrease (P = .16). However, there was a significant inverse association between minimum postoperative mean arterial pressure and infection, with an estimated odds ratio of 1.08 (1.03–1.12) per 5-mm Hg decrease (P = .001).

CONCLUSIONS:
Postoperative time-weighted mean arterial pressure was not associated with surgical site infection, but lowest postoperative mean arterial pressure was. Whether the relationship is causal remains to be determined.
World Health Organization Surgical Safety Checklist: Compliance and Associated Surgical Outcomes in Uganda’s Referral Hospitals
Authors: Igaga Elizabeth N. , Sendagire Cornelius , Kizito Samuel , Obua Daniel , Kwizera Arthur 
Published: July 2018

BACKGROUND:
A pilot study on the World Health Organization (WHO) Surgical Safety Checklist (SSC) showed a reduction in both major complications and mortality of surgical patients. Compliance with this checklist varies around the world. We aimed to determine the extent of compliance with the WHO SSC and its association with surgical outcomes in 5 of Uganda’s referral hospitals.

METHODS:
A multicentre prospective cohort study was conducted in 5 referral hospitals in Uganda. Using a questionnaire based on the WHO SSC, patients undergoing surgical operations were systematically recruited into the study from April 2016 to July 2016. The patients were followed up daily for 30 days or until discharge for the purpose of documentation of complications. Logistic regression and linear regression were used to assess for association between compliance and perioperative surgical outcomes.

RESULTS:
We recruited 859 patients into the study. Overall compliance with the WHO SSC was 41.7% (95% confidence interval [CI], 39.7–43.8) ranging from 11.9% to 89.8% across the different hospitals. Overall compliance with “sign in” was 44.7% (95% CI, 43–45.6), with “time out” was 42.0% (95% CI, 39.4–44.6), and with “sign out” was 33.3% (95% CI, 30.7–35.9). There was no association between compliance and perioperative surgical outcomes: length of hospital stay, adverse events, and mortality.

CONCLUSIONS:
This study revealed low levels of compliance with the WHO SSC. There was a statistically significant association between this level of compliance and the incidence of pain and loss of consciousness postoperatively.
Literary History Meets the History of Reading
Authors: Turnovsky Geoffrey 
Published: July 2018

Abstract
This article revisits the letters written by readers of the Mercure galant who responded to the “gallant question,” posed by the periodical's editor in an April 1678 issue, regarding a central plot twist of Madame de Lafayette's novel La Princesse de Clèves. Highlighting the expansive, democratic, and participatory nature of this readership that connected with the unprecedented complexity of the novel's characters, scholars have imputed to this public a modernity reflecting that of the novel itself, often considered “the first modern novel” in French. Closely analyzing the letters in light of their arguments and of the novel's editorial history, this essay explores the implications of a disconnect between the work and the readers in question, who had perhaps not read the text and did not, in any case, empathize with its protagonist's dilemma as presented by the Mercure.
Atuação do Assistente Social no Núcleo de Assistência à Saúde Familiar: reflexões sobre o acompanhamento e monitoramento no município de Dormentes- Pernambuco, Brasil
Authors: Macedo Maria Liberácia , Góes Claudemar Pimenta G 
Published: July 2018

A atuação do profissional formado em Serviço Social apresenta possibilidades de operacionalização para as políticas públicas, com o escopo de planejamento, gestão e a execução de políticas, programas, projetos e serviços sociais. Porém, destaca-se neste artigo, o campo de conhecimento na área de saúde. Nesta perspectiva, o profissional em Serviço Social tem integrado equipes multidisciplinares de acompanhamento, monitoramento e controle, posto que, o modelo anterior de assistência à saúde cede espaço para adequações e transformações sociais e culturais. Dada a incipiência de estudos na área, o presente estudo tem como objetivo central a investigação do processo de inclusão do Assistente Social nos Núcleos de Atendimento à Saúde da Família (NASF), assim como a evolução do quantitativo de profissionais entre 2008 e 2018, considerando as articulações públicas desenvolvidas no município de Dormentes – PE.
Tratamento medicamentoso: conhecimento de usuários em clínica-escola
Authors: De Freitas Teresa Maria Barbosa Leal , De Freitas Mariélia Barbosa Leal , Marques Rosemarie Brandim 
Published: July 2018

O nível de conhecimento farmacológico é fundamental para o sucesso do tratamento medicamentoso. O objetivo foi avaliar o grau de conhecimento de pacientes atendidos no Ambulatório de uma Instituição de Ensino Superior Privado quanto ao tratamento farmacológico, após consulta e dispensação medicamentosa. Foi um estudo transversal, com abordagem quantitativa, realizada entre março e setembro de 2013, com 40 pacientes. Foram 67,5% de mulheres com idade média de 56,4 ± 13 anos. O grau de escolaridade foi 32,5% de analfabetos, 62,5% com renda familiar de até um salário-mínimo. O nível de conhecimento medicamentoso foi bom (10,0%), 57,5% regular nível de informação a respeito do medicamento prescrito, conhecimento insuficiente de 32,5%. 60,0% dos pacientes após consulta e dispensação medicamentosa tiveram baixo grau de adesão. Faz-se necessário implementar ações educativas com equipe multidisciplinar com os pacientes e a presença do profissional farmacêutico para melhor orientar os mesmos quanto ao uso correto de medicamentos.
As Políticas Educacionais e a Interface Neoliberal: A educação como um “Tesouro a descobrir”
Authors: Sindeaux Rebeca Baia , Bezerra Francisco Wellery Gomes , Loureiro Maria Dulcinea Silva 
Published: July 2018

Partindo da premissa de que o capitalismo tem a capacidade de, em momentos de crise, se erguer com mais força, este artigo se dispôs a analisar em que medida a crise contemporânea interfere na implantação de políticas educacionais na periferia do capital. Para garantir o processo de reestruturação os capitalistas recorreram às políticas neoliberais, em que se exigia um tipo de trabalhador que atendesse as novas demandas produtivas. Neste cenário contemporâneo de crise, as determinações oriundas da agenda do capital internacional para educação, mais especificamente formuladas a partir de 1990 pela Conferência Mundial de Educação para Todos, patrocinada pelo Banco Mundial, podem ser consideradas como o marco na busca pelo ajuste da educação às necessidades do mercado, diante de um processo de reestruturação produtiva. Esse artigo faz uma revisão de literatura de obras que tratam dos impactos pós Conferência Mundial de Educação Para Todos na educação dos países da periferia do capital. As considerações deste artigo apontam para uma reflexão sobre como a “desejada” redução do Estado passa necessariamente pela conversão da Educação de um direito social a um serviço, o que atende aos interesses do capital financeiro como estratégia política de manutenção de um modo de produção pautado no consumo.