bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGFR3 Translocations in Bladder Cancer: Differential Sensitivity to HSP90 Inhibition Based on Drug Metabolism
Authors: Acquaviva Jaime , He Suqin , Zhang Chaohua , Jimenez John-Paul , Nagai Masazumi , Sang Jim , Sequeira Manuel , Smith Donald L. , Ogawa Luisa Shin , Inoue Takayo , Tatsuta Noriaki , Knowles Margaret A. , Bates Richard C. , Proia David A. 
Published: May 2014

Abstract
Activating mutations and/or overexpression of FGFR3 are common in bladder cancer, making FGFR3 an attractive therapeutic target in this disease. In addition, FGFR3 gene rearrangements have recently been described that define a unique subset of bladder tumors. Here, a selective HSP90 inhibitor, ganetespib, induced loss of FGFR3-TACC3 fusion protein expression and depletion of multiple oncogenic signaling proteins in RT112 bladder cells, resulting in potent cytotoxicity comparable with the pan-FGFR tyrosine kinase inhibitor BGJ398. However, in contrast to BGJ398, ganetespib exerted pleiotropic effects on additional mitogenic and survival pathways and could overcome the FGFR inhibitor–resistant phenotype of FGFR3 mutant–expressing 97-7 and MHG-U3 cells. Combinatorial benefit was observed when ganetespib was used with BGJ398 both in vitro and in vivo. Interestingly, two additional FGFR3 fusion-positive lines (RT4 and SW480) retained sensitivity to HSP90 inhibitor treatment by the ansamycins 17-AAG and 17-DMAG yet displayed intrinsic resistance to ganetespib or AUY922, both second-generation resorcinol-based compounds. Both cell lines, compared with RT112, expressed considerably higher levels of endogenous UGT1A enzyme; this phenotype resulted in a rapid glucuronidation-dependent metabolism and subsequent efflux of ganetespib from SW780 cells, thus providing a mechanism to account for the lack of bioactivity.
Implications: Pharmacologic blockade of the molecular chaperone HSP90 represents a promising approach for treating bladder tumors driven by oncogenic gene rearrangements of FGFR3. Furthermore, UDP-glucuronosyltransferase enzyme expression may serve as a predictive factor for clinical response to resorcinol-based HSP90 inhibitors. Mol Cancer Res; 12(7); 1042–54. ©2014 AACR.
Cooperativity of E-cadherin and Smad4 Loss to Promote Diffuse-Type Gastric Adenocarcinoma and Metastasis
Authors: Park Jun Won , Jang Seok Hoon , Park Dong Min , Lim Na Jung , Deng Chuxia , Kim Dae Yong , Green Jeffrey E. , Kim Hark Kyun 
Published: May 2014

Abstract
Loss of E-cadherin (CDH1), Smad4, and p53 has been shown to play an integral role in gastric, intestinal, and breast cancer formation. Compound conditional knockout mice for Smad4, p53, and E-cadherin were generated to define and compare the roles of these genes in gastric, intestinal, and breast cancer development by crossing with Pdx-1-Cre, Villin-Cre, and MMTV-Cre transgenic mice. Interestingly, gastric adenocarcinoma was significantly more frequent in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice than in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1+/+ mice, demonstrating that Cdh1 heterozygosity accelerates the development and progression of gastric adenocarcinoma, in combination with loss of Smad4 and p53. Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice developed gastric adenocarcinomas without E-cadherin expression. However, intestinal and mammary adenocarcinomas with the same genetic background retained E-cadherin expression and were phenotypically similar to mice with both wild-type Cdh1 alleles. Lung metastases were identified in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice, but not in the other genotypes. Nuclear β-catenin accumulation was identified at the invasive tumor front of gastric adenocarcinomas arising in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice. This phenotype was less prominent in mice with intact E-cadherin or Smad4, indicating that the inhibition of β-catenin signaling by E-cadherin or Smad4 downregulates signaling pathways involved in metastases in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice. Knockdown of β-catenin significantly inhibited the migratory activity of Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ cell lines. Thus, loss of E-cadherin and Smad4 cooperates with p53 loss to promote the development and metastatic progression of gastric adenocarcinomas, with similarities to human gastric adenocarcinoma.
Implications: This study demonstrates that inhibition of β-catenin is a converging node for the antimetastatic signaling pathways driven by E-cadherin and Smad4 in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice, providing novel insights into mechanisms for gastric cancer metastasis. Mol Cancer Res; 12(8); 1088–99. ©2014 AACR.
Effects of Sex on Coronary Microvascular Dysfunction and Cardiac Outcomes
Authors: Murthy Venkatesh L. , Naya Masanao , Taqueti Viviany R. , Foster Courtney R. , Gaber Mariya , Hainer Jon , Dorbala Sharmila , Blankstein Ron , Rimoldi Ornella , Camici Paolo G. , Di Carli Marcelo F. 
Published: May 2014

Background—
Coronary microvascular dysfunction (CMD) is a prevalent and prognostically important finding in patients with symptoms suggestive of coronary artery disease. The relative extent to which CMD affects both sexes is largely unknown.

Methods and Results—

We investigated 405 men and 813 women who were referred for evaluation of suspected coronary artery disease with no previous history of coronary artery disease and no visual evidence of coronary artery disease on rest/stress positron emission tomography myocardial perfusion imaging. Coronary flow reserve was quantified, and coronary flow reserve <2.0 was used to define the presence of CMD. Major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, late revascularization, and hospitalization for heart failure, were assessed in a blinded fashion over a median follow-up of 1.3 years (interquartile range, 0.5–2.3 years). CMD was highly prevalent both in men and women (51% and 54%, respectively; Fisher exact test =0.39; equivalence
P
=0.0002). Regardless of sex, coronary flow reserve was a powerful incremental predictor of major adverse cardiac events (hazard ratio, 0.80 [95% confidence interval, 0.75–086] per 10% increase in coronary flow reserve;
P
<0.0001) and resulted in favorable net reclassification improvement (0.280 [95% confidence interval, 0.049–0.512]), after adjustment for clinical risk and ventricular function. In a subgroup (n=404; 307 women/97 men) without evidence of coronary artery calcification on gated computed tomography imaging, CMD was common in both sexes, despite normal stress perfusion imaging and no coronary artery calcification (44% of men versus 48% of women; Fisher exact test
P
=0.56; equivalence
P
=0.041).

Conclusions—
CMD is highly prevalent among at-risk individuals and is associated with adverse outcomes regardless of sex. The high prevalence of CMD in both sexes suggests that it may be a useful target for future therapeutic interventions.
Impact of Dispatcher‐Assisted Bystander Cardiopulmonary Resuscitation on Neurological Outcomes in Children With Out‐of‐Hospital Cardiac Arrests: A Prospective, Nationwide, Population‐Based Cohort Study
Authors: Goto Yoshikazu , Maeda Tetsuo , Goto Yumiko 
Published: May 2014

Background

The impact of dispatcher‐assisted bystander cardiopulmonary resuscitation (
CPR
) on neurological outcomes in children is unclear. We investigated whether dispatcher‐assisted bystander
CPR
shows favorable neurological outcomes (Cerebral Performance Category scale 1 or 2) in children with out‐of‐hospital cardiac arrest (
OHCA
).

Methods and Results

Children (n=5009, age<18 years) with
OHCA
were selected from a nationwide Utstein‐style Japanese database (2008–2010) and divided into 3 groups: no bystander
CPR
(n=2287); bystander
CPR
with dispatcher instruction (n=2019); and bystander CPR without dispatcher instruction (n=703) groups. The primary endpoint was favorable neurological outcome at 1 month post‐
OHCA
. Dispatcher
CPR
instruction was offered to 53.9% of patients, significantly increasing bystander
CPR
provision rate (adjusted odds ratio [
aOR
], 7.51; 95% confidence interval [
CI
], 6.60 to 8.57). Bystander CPR with and without dispatcher instruction were significantly associated with improved 1‐month favorable neurological outcomes (aOR, 1.81 and 1.68; 95% CI, 1.24 to 2.67 and 1.07 to 2.62, respectively), compared to no bystander CPR. Conventional CPR was associated with increased odds of 1‐month favorable neurological outcomes irrespective of etiology of cardiac arrest (
aOR
, 2.30; 95% CI, 1.56 to 3.41). However, chest‐compression‐only CPR was not associated with 1‐month meaningful outcomes (
aOR
, 1.05; 95%
CI
, 0.67 to 1.64).

Conclusions

In children with
OHCA
, dispatcher‐assisted bystander
CPR
increased bystander
CPR
provision rate and was associated with improved 1‐month favorable neurological outcomes, compared to no bystander
CPR
. Conventional bystander
CPR
was associated with greater likelihood of neurologically intact survival, compared to chest‐compression‐only
CPR,
irrespective of cardiac arrest etiology.
Survivors of brain injury: The narrative experiences of being a college or university student
Authors: Cahill Susan M. , Rotter Jamie M. , Lyons Kara K. , Marrone Antonina R. 
Published: May 2014

Background. The deficits associated with a brain injury may pose many challenges to young adult students. Purpose. The purpose of this study was to conduct an in-depth exploration of the experiences and processes individuals who self-identify as having a brain injury go through during college or university to overcome obstacles. Method. This study used a basic interpretative qualitative design. Data were collected through semi-structured interviews and analyzed with the constant comparative method. Findings. Three themes emerged: balancing act, reality versus injury, and square peg in a round hole. Participants discussed personal strategies that they used to help them be successful. Despite these strategies, the participants continued to feel out of place and felt that seeking disability services would further set them apart from their non-injured peers. Implications. Individuals post–brain injury may benefit from occupational therapy services to reduce the challenges associated with functioning in the student role in college and university environments.
Exploring the nexus between health promotion and occupational therapy: Synergies and similarities
Authors: Tucker Patricia , Vanderloo Leigh M. , Irwin Jennifer D. , Mandich Angela D. , Bossers Ann M. 
Published: May 2014

Background. The similarities between health promotion and occupational therapy have been recognized. Both are based on perspectives that share a goal of enabling individuals and populations to improve control over their health. Consequently, it is logical that the principles of health promotion complement the practice of occupational therapy. Purpose. This paper highlights the affinity between occupational therapy and health promotion, and discusses ways in which health promotion principles can be incorporated into occupational therapy practice. Key Issues. Some Canadian occupational therapists may be unaware of the current discourse in health promotion and, thus, may not be incorporating its principles into practice. Steps are warranted to expand the current knowledge and practice of therapists to include health promotion, with specific attention to providing services for the population. Implications. Incorporating health promotion principles into occupational therapy perspectives will facilitate the implementation of the domains of practice within the occupational therapy profile. This paper highlights how the principles of health promotion can impact practice at the individual and community level.
Prevalence of the hospitalisation of mentally ill offenders in the Forensic Unit of the Clinic of Psychiatry in Pristina over a three-year period and long-term strategy implications for the management of the Forensic Mental Health System Service
Authors: Ibishi Nazmie F , Musliu Nebi R , Hundozi Zylfije , Citaku Kaltrina 
Published: May 2014

Background As a new field in our country, forensic psychiatry needs strategies for management and rehabilitation programmes. Aim The aim of this study was to evaluate the sociodemographic characteristics of psychiatrically diagnosed inpatients who were hospitalised in the three years from January 2009 to December 2011 and the prevalence of such diagnoses. The specific objectives of this study were to use our results to identify rehabilitation programmes for the treatment of patients and to identify the specific training needs of mental-health professionals. Methods In this retrospective study, we collected data about the sociodemographics and violent behaviour of all forensic inpatients who underwent court-ordered psychiatric forensic evaluation and assessment. We reviewed and studied the documented diagnoses based on the following criteria and sources: the ICD-10 criteria for mental disorders, the Structured Clinical Interview (SCID), recidivism rates, criminal data, court records and other hetero-anamnesis data. The data were analysed using a descriptive approach. Results The subjects were referred for forensic psychiatric evaluation, diagnosis and treatment either directly from prison (23.2%) or from the court (76.8%). The majority of the offenders (85.7%) were currently on trial, and charges of physically threatening others were more common than charges of domestic violence or murder. The prevalence of psychiatric diagnosis was 94.6%, and the most common diagnosis was psychosis (69.1%). Drug abuse and personality disorders, including high-risk behaviours, were also common. The overall relapse rate for aggressive behaviour was 48.9%. Conclusion Rehabilitation programmes for treatment and management are needed that specifically focus on psychotic disorders, severe personality disorders and drug abuse.
Evaluation of a Telerobotic System for Transnasal Surgery of the Larynx and Airways in Cadavers
Authors: Dharamsi Latif M. , Bajo Andrea , Netterville James L. , Garrett C. Gaelyn , Simaan Nabil 
Published: May 2014

ObjectivesMinimally invasive, transnasal endoscopic approaches to the larynx have been utilized but are limited by the precision and accuracy afforded to the surgeon. The objective of this study is to analyze the feasibility of a rapidly deployable telerobotic system for enabling transnasal microsurgery of the larynx and upper airways, specifically injection laryngoplasty.Study DesignThis is a feasibility study.SettingThis study was conducted at a laboratory in the Department of Mechanical Engineering at Vanderbilt University.Subjects and MethodsA feasibility study was conducted in which a telerobotic system was transnasally inserted in both a human intubation trainer mannequin and a cadaver. A flexible needle was passed through an instrumentation port and targeted specific areas of the vocal folds of our models to simulate injection laryngoplasty. The experiments were recorded with both still and video photography. Average forces exerted on surrounding tissue and times of deployment were measured.ResultsOur robot was able to expeditiously gain access to the glottis with an average manual insertion time of 5.87 seconds while exerting minimal forces on the surrounding tissues with an average force of 4.45 Newtons. The onboard fiberoptic endoscope conveyed images of adequate quality for the completion of a simulated injection medialization laryngoplasty. The experiment was successfully completed in both mannequin and cadaveric models.ConclusionThis telerobotic system proved to be capable of being rapidly deployed to the upper airways while exerting minimal forces to the surrounding structures and successfully simulated injection medialization laryngoplasty.
Two-year follow-up of first human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence
Authors: Almeida Jose I , Javier Julian J , Mackay Edward G , Bautista Claudia , Cher Daniel J , Proebstle Thomas M 
Published: May 2014

Objectives To evaluate the safety and effectiveness of endovenous cyanoacrylate-based embolization of incompetent great saphenous veins. Methods Incompetent great saphenous veins in 38 patients were embolized by cyanoacrylate bolus injections under ultrasound guidance without the use of perivenous tumescent anesthesia or graduated compression stockings. Follow-up was performed over a period of 24 months. Result Of 38 enrolled patients, 36 were available at 12 months and 24 were available at 24 months follow-up. Complete occlusion of the treated great saphenous vein was confirmed by duplex ultrasound in all patients except for one complete and two partial recanalizations observed at, 1, 3 and 6 months of follow-up, respectively. Kaplan-Meier analysis yielded an occlusion rate of 92.0% (95% CI 0.836–1.0) at 24 months follow-up. Venous Clinical Severity Score improved in all patients from a mean of 6.1 ± 2.7 at baseline to 1.3 ± 1.1, 1.5 ± 1.4 and 2.7 ± 2.5 at 6, 12 and 24 months, respectively ( p < .0001). Edema improved in 89% of legs (n = 34) at 48 hours follow-up. At baseline, only 13% were free from pain. At 6, 12 and 24 months, 84%, 78% and 64% were free from leg pain, respectively. Conclusions The first human use of endovenous cyanoacrylate for closure of insufficient great saphenous veins proved to be feasible, safe and effective. Clinical efficacy was maintained over a period of 24 months.
Self-management interventions for chronic disease: a systematic scoping review
Authors: Richardson Julie , Loyola-Sanchez Adalberto , Sinclair Susanne , Harris Jocelyn , Letts Lori , MacIntyre Norma J , Wilkins Seanne , Burgos-Martinez Gabriela , Wishart Laurie , McBay Cathy , Martin Ginis Kathleen 
Published: May 2014

Objective: To investigate the contributions of physiotherapy and occupational therapy to self-management interventions and the theoretical models used to support these interventions in chronic disease. Data sources: We conducted two literature searches to identify studies that evaluated self-management interventions involving physiotherapists and occupational therapists in MEDLINE, the Cochrane Library, CINAHL, EMBASE, AMED (Allied and Complementary Medicine), SPORTdiscus, and REHABDATA databases. Study selection: Four investigator pairs screened article title and abstract, then full text with inclusion criteria. Selected articles ( n = 57) included adults who received a chronic disease self-management intervention, developed or delivered by a physiotherapist and/or an occupational therapist compared with a control group. Data extraction: Four pairs of investigators performed independent reviews of each article and data extraction included: (a) participant characteristics, (b) the self-management intervention, (c) the comparison intervention, (d) outcome measures, construct measured and results. Data synthesis: A total of 47 articles reported the involvement of physiotherapy in self-management compared with 10 occupational therapy articles. The type of chronic condition produced different yields: arthritis n = 21 articles; chronic obstructive pulmonary disease and chronic pain n = 9 articles each. The theoretical frameworks most frequently cited were social cognitive theory and self-efficacy theory. Physical activity was the predominant focus of the self-management interventions. Physiotherapy programmes included disease-specific education, fatigue, posture, and pain management, while occupational therapists concentrated on joint protection, fatigue, and stress management. Conclusions: Physiotherapists and occupational therapists make moderate contributions to self-management interventions. Most of these interventions are disease-specific and are most frequently based on the principles of behaviour change theories.
Effect of Anticipation on Lower Extremity Biomechanics During Side- and Cross-Cutting Maneuvers in Young Soccer Players
Authors: Kim Jin Hyun , Lee Ki-Kwang , Kong Se Jin , An Keun Ok , Jeong Jin Hwa , Lee Yong Seuk 
Published: May 2014

Background: Less mature athletes exhibit biomechanical parameters during cutting maneuvers that may place these athletes at greater risk for injury than their more mature counterparts, especially if the maneuvers are unanticipated. However, most studies on risk factors for anterior cruciate ligament (ACL) injury have focused on neuromuscular and knee kinematic differences between the sexes, not on the biomechanical parameters between specific sporting maneuvers. Hypotheses: (1) Anticipation will have a greater effect than the type of cutting maneuver (side- vs cross-cutting) in terms of the biomechanical risk factors for ACL injuries, and (2) the biomechanical risk factors will be different between the 2 types of maneuvers. Study Design: Controlled laboratory study. Methods: Thirty-seven young, male middle school soccer players participated in this study. Three-dimensional motion analysis featuring ground-reaction force and electromyography of the right leg was used. Kinematics, kinetics, and electromyography data for each athlete were analyzed during anticipated and unanticipated side- and cross-cutting maneuvers. The differences between anticipated and unanticipated states as well as between side- and cross-cutting maneuvers were calculated and compared. Results: After unanticipated side-cutting, the time to peak ground-reaction force was longer and peak values were smaller compared with anticipated side-cutting. Flexion, valgus, and internal rotations in the knee joint were larger, and greater flexion and valgus moments were observed. The vastus lateralis and vastus medialis showed lower activity, and the lateral gastrocnemius showed higher activity after unanticipated side-cutting maneuvers. With unanticipated cross-cutting, the time to peak ground-reaction force was longer and peak values were smaller compared with anticipated cross-cutting, and the lateral gastrocnemius showed higher activity. Differences in the peak values of the mediolateral and vertical forces were smaller in the cross-cutting maneuver than in side-cutting. Changes in flexion and adduction of the hip joint, flexion of the knee joint, and inversion of the ankle joint were larger during side-cutting. Conclusion: Although there were some interactions between direction and anticipation, anticipating a cutting maneuver generally had a greater effect than the type of maneuver when there was no significant interaction. Clinical Relevance: Increases in the valgus angle and moment of the knee joint and higher lateral gastrocnemius activity during the late period showed an association with ACL injury risk factors during side-cutting, and higher lateral gastrocnemius activity during the early period showed an association with injury risk factors during cross-cutting.