bluuebunny/crossref_metadata_2025_split huggingface dataset:
KLF5 Regulates the Integrity and Oncogenicity of Intestinal Stem Cells
Authors: Nakaya Takeo , Ogawa Seishi , Manabe Ichiro , Tanaka Masami , Sanada Masashi , Sato Toshiro , Taketo Makoto M. , Nakao Kazuki , Clevers Hans , Fukayama Masashi , Kuroda Masahiko , Nagai Ryozo 
Published: March 2014

Abstract
The intestinal epithelium maintains homeostasis by a self-renewal process involving resident stem cells, including Lgr5+ crypt-base columnar cells, but core mechanisms and their contributions to intestinal cancer are not fully defined. In this study, we examined a hypothesized role for KLF5, a zinc-finger transcription factor that is critical to maintain the integrity of embryonic and induced pluripotent stem cells, in intestinal stem-cell integrity and cancer in the mouse. Klf5 was indispensable for the integrity and oncogenic transformation of intestinal stem cells. In mice, inducible deletion of Klf5 in Lgr5+ stem cells suppressed their proliferation and survival in a manner associated with nuclear localization of β-catenin (Catnb), generating abnormal apoptotic cells in intestinal crypts. Moreover, production of lethal adenomas and carcinomas by specific expression of an oncogenic mutant of β-catenin in Lgr5+ stem cells was suppressed completely by Klf5 deletion in the same cells. Given that activation of the Wnt/β-catenin pathway is the most frequently altered pathway in human colorectal cancer, our results argue that KLF5 acts as a fundamental core regulator of intestinal oncogenesis at the stem-cell level, and they suggest KLF5 targeting as a rational strategy to eradicate stem-like cells in colorectal cancer. Cancer Res; 74(10); 2882–91. ©2014 AACR.
Developing Precision Medicine in a Global World
Authors: Rubin Eric H. , Allen Jeffrey D. , Nowak Jan A. , Bates Susan E. 
Published: March 2014

Abstract
Advances in understanding the biology of cancer, as well as advances in diagnostic technologies, such as the advent of affordable high-resolution DNA sequencing, have had a major impact on the approach to identification of specific alterations in a given patient's cancer that could be used as a basis for treatment selection, and hence the development of companion diagnostics. Although there are now several examples of successful development of companion diagnostics that allow identification of patients who will achieve the greatest benefit from a new therapeutic, the path to coapproval of a diagnostic test along with a new therapeutic is complex and often inefficient. This review and the accompanying articles examine the current state of companion diagnostic development in the United States and Europe from academic, industry, regulatory, and economic perspectives.
See all articles in this CCR Focus section, “The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development.”
Clin Cancer Res; 20(6); 1419–27. ©2014 AACR.
Predictive Factors for Pharyngocutaneous Fistulization After Total Laryngectomy
Authors: Timmermans Adriana J. , Lansaat Liset , Theunissen Eleonoor A. R. , Hamming-Vrieze Olga , Hilgers Frans J. M. , van den Brekel Michiel W. M. 
Published: March 2014

Objectives: Postoperative complications, especially pharyngocutaneous fistulization (PCF), are more frequent after total laryngectomy (TL) performed for salvage after (chemo)radiotherapy than after primary TL. The aim of this study was to identify the incidence of PCF, predictive factors for PCF, and the relationship of PCF to survival. Methods: We performed a retrospective chart review of 217 consecutive patients treated with TL between 2000 and 2010. Univariate and multivariable analysis with logistic regression was used to identify factors associated with PCF. We used a Kaplan-Meier survival analysis. Results: The overall incidence of PCF was 26.3% (57 of 217 cases). The incidence of PCF after primary TL was 17.1% (12 of 70), that after salvage TL was 25.5% (25 of 98), that after TLE for a second primary was 37.5% (9 of 24), and that after TL for a dysfunctional larynx was 44.0% (11 of 25). The predictive factors for PCF were hypopharynx cancer (odds ratio [OR], 3.67; 95% confidence interval [CI], 1.74 to 7.71; P = .001), an albumin level of less than 40 g/L (OR, 2.20; 95% CI, 1.12 to 4.33; P = .022), previous chemoradiotherapy (OR, 3.38; 95% CI, 1.34 to 8.52; P = .010), more-extended pharyngeal resection ( P = .001), and pharynx reconstruction ( P = .002). The median duration of survival was 30 months (95% CI, 17.5 to 42.5); the 2-year overall survival rate was 54%. The median duration of survival of patients with PCF was 23 months (95% CI, 9.4 to 36.6), and that of those without PCF was 31 months (95% CI, 15.0 to 47.0; P = .421). The 2-year overall survival rate was 48% in patients with PCF and 57% in those without PCF ( P = .290). Conclusions: Incidence of PCF after TL is significantly higher in patients with hypopharynx cancer, previous chemoradiotherapy, a low albumin level, more-extended pharyngeal resection, or pharynx reconstruction. The occurrence of PCF does not influence the rate of survival.
Vestibular Neurolabyrinthitis
Authors: Magliulo Giuseppe , Gagliardi Silvia , Appiani Mario Ciniglio , Iannella Giannicola , Re Massimo 
Published: March 2014

Objectives: The aim of this study was to evaluate prospectively, in a group of patients affected by vestibular neurolabyrinthitis (VN), a diagnostic protocol including cervical vestibular evoked myogenic potentials (C-VEMPs), ocular vestibular evoked myogenic potentials (O-VEMPs), and the video head impulse test (vHIT). Methods: The diagnosis of VN was based on the patient’s clinical history, an absence of associated auditory or neurologic symptoms, and a neuro-otological examination with an evaluation of lateral semicircular canal function by use of the Fitzgerald-Hallpike caloric vestibular test and the ice test. Results: In our series, 55% of the cases were superior and inferior VN, 40% were superior VN, and 5% were inferior VN. These cases, however, comprised different degrees of vestibular involvement, as the individual vestibular end organs have different prognoses. Four patients had only deficits of the horizontal and superior semicircular canals or their ampullary nerves. Conclusions: The implementation of C-VEMPs, O-VEMPs, and the vHIT in a vestibular diagnostic protocol has made it possible to observe patients with ampullary VN in a way that has not been feasible with other types of vestibular examinations. The age of the patient seems to have some impact on recovery from VN. When recovery occurs in the utricular and saccular nerves first and in the ampullary nerves subsequently, it may be reasonable to expect a more favorable outcome.
High-Dose Sublesional Bevacizumab (Avastin) for Pediatric Recurrent Respiratory Papillomatosis
Authors: Sidell Douglas R. , Nassar Michel , Cotton Robin T. , Zeitels Steven M. , de Alarcon Alessandro 
Published: March 2014

Objectives: We review and report the use of high-dose bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP) in pediatric patients. Methods: We included all patients with pediatric-onset RRP who underwent bevacizumab (25 mg/mL) injections by a single practitioner. A series of 5 consecutive subepithelial injections were administered at 4- to 6-week intervals with concomitant 532 nm KTP laser ablation. The lesions were staged according to the Derkay staging system. The outcomes included pretreatment and posttreatment Derkay scores, the time interval between procedures, and voice outcomes. The demographic data extracted included sex, age at diagnosis, and current age. Results: Nine patients were included in this study, with 1 patient lost to follow-up; their median age was 8 years (range, 3 to 21 years). The mean bevacizumab dose was 14.25 mg (range, 5 to 45 mg). There was a median Derkay score of 11.5 (range, 4 to 23) at the time of diagnosis and a median 58% improvement following therapy. All patients demonstrated an increased time interval between injections, for a median improvement of 2.05× (range, 1.6× to 3.25×). Conclusions: Evidence exists in support of vascular endothelial growth factor as an important factor in the development of RRP. Although some variability in response is demonstrated by this study, high-dose bevacizumab appears to yield promising results for pediatric patients with RRP.
Satisfaction Level and Perception of Quality in Cancer Care
Authors: Sharma Kuldeep , Kataria Tejinder , Bisht Shyam Singh , Goyal Shikha , Gupta Deepak 
Published: March 2014

Consumer’s perception of health care quality and his satisfaction is being identified as an important issue in health care industry. Studies addressing patients’ perceptions of quality are available but there is paucity of data regarding the perception of health care providers (service-providers) towards their own services. This study was undertaken to compare the satisfaction level between the patients and health care providers from a radiation oncology department. A common 16-item questionnaire was served to 40 patients and 40 staff members. The responses were statistically evaluated to assess the satisfaction level among the two groups and the scores were compared to assess the agreement between two groups. Overall, satisfaction level of both groups regarding quality of services ranged from ‘good’ to ‘excellent’. A high level of agreement was observed between the two groups. The physician’s ability to give explanation to patients, helping attitude of the staff and the staff’s concern for patient safety were the most satisfying features of the department while inconvenience during scheduling of appointments, billing and registration process, status of the changing rooms and inter-department coordination were the least satisfying features. A high level of satisfaction may be achieved from the consumers if service providers are trained to assess the needs and expectations of consumers and to critically evaluate themselves. The service-providers’ perception regarding their own services may serve as a preliminary indicator of overall quality. Future studies in different settings with more number of patients may further explore our results.
Development of Primary Health Care Systems and MCH Services in Karnataka
Authors: Bhat T. N. 
Published: March 2014

The present study examined the performance of MCH programmes relative to the development of primary health care systems in Karnataka state. The study focused its analysis on the institutional development of primary health care systems, namely, Sub-Centres (SCs), Primary Health Centres (PHCs) and Community Health Centres (CHCs) in terms of expansion and populations served by these facilities during the past three decades consequent to adoption of ‘Health for All by 2000’ strategy, and performance of MCH services in the past 20 years with respect to key components. The study finds that the primary health care systems in Karnataka are not only intensively developed in comparison to the country as a whole but also on similar levels with other South Indian states. The health facilities in Malnad and coastal districts are more evenly and intensively developed than in other regions. The facilities in many taluks of Hyderabad Karnataka are burdened with much higher population coverage than the specified population norms, particularly with respect to SCs and PHCs. Karnataka is far behind the goals set by the NPP of 2000 in the performance of MCH indicators as compared to Kerala and Tamil Nadu states. The population parameters specified by the NPP-2000 for the creation of SCs and PHCs were almost achieved in the state within a decade of expansion drive, that is, during 1990–91. The overall progress of MCH performance in Karnataka is, however not in tandem with the extent of expansion in health facilities. The process of progress in MCH programmes in the state appears to be staggered by low and sluggish performances in Mumbai and Hyderabad Karnataka districts. More health facilities, specifically, SCs and PHCs may be created in Hyderabad and Mumbai Karnataka districts.
Recurrent metastatic anal cancer treated with modified paclitaxel, ifosfamide, and cisplatin and third-line mitomycin/cetuximab
Authors: Khawandanah Mohamad , Baxley Allison , Pant Shubham 
Published: March 2014

Purpose Squamous cell carcinoma represents approximately 75% of all anal cancers. Squamous cell carcinoma of the anal canal is a rare malignancy often curable in the early stages with the combined modality therapy of chemoradiation. Treatment in the metastatic setting is challenging due to the rarity of metastatic disease with the majority of patients presenting with curative locally advanced disease, and the ability to design clinical trials for metastatic disease has yet to be explored. There are no established chemotherapy guidelines for patients with metastatic anal cancer after the failure of cisplatin and fluorouracil. Methods We used PubMed and OVID research engines to identify publications in English literature addressing treatments/therapeutics using the following keywords “metastatic anal cancer” and “metastatic squamous cell carcinoma of anus” in addition to reviewing related clinical trials in clinicaltrials.gov. Results We hereby report our experience in using aggressive combinations in the second- and third-line settings. A 49-year-old white male diagnosed with T3 N3 M0 Stage IIIB anal cancer was treated initially with surgical excision and adjuvant fluorouracil/cisplatin due unavailability of mitomycin. He developed metastatic disease to the skin and perianal region, was treated with four cycles of paclitaxel, ifosfamide, and cisplatin with growth factor support, and achieved minimal residual disease. On progression five months after finishing therapy, we treated him with mitomycin and cetuximab with mixed response after two cycles. The patient later elected to proceed with hospice care only and succumbed to his disease 16 months after first cycle of paclitaxel, ifosfamide, and cisplatin and 24 months from diagnosis. Conclusions Paclitaxel, ifosfamide, and cisplatin is highly active in metastatic setting in selected patients. Cetuximab based regimen can be valuable option as second or third line. Paclitaxel, ifosfamide, and cisplatin and mitomycin and cetuximab can be available options for unmet need in metastatic anal cancer.
Performance evaluation of a health insurance in Nigeria using optimal resource use: health care providers perspectives
Authors: Mohammed Shafiu , Souares Aurélia , Bermejo Justo Lorenzo , Sauerborn Rainer , Dong Hengjin 
Published: March 2014

Abstract

Background
Performance measures are often neglected during the transition period of national health insurance scheme implementation in many low and middle income countries. These measurements evaluate the extent to which various aspects of the schemes meet their key objectives. This study assesses the implementation of a health insurance scheme using optimal resource use domains and examines possible factors that influence each domain, according to providers’ perspectives.

Methods
A retrospective, cross-sectional survey was done between August and December 2010 in Kaduna state, and 466 health care provider personnel were interviewed. Optimal-resource-use was defined in four domains: provider payment mechanism (capitation and fee-for-service payment methods), benefit package, administrative efficiency, and active monitoring mechanism. Logistic regression analysis was used to identify provider factors that may influence each domain.

Results
In the provider payment mechanism domain, capitation payment method (95%) performed better than fee-for-service payment method (62%). Benefit package domain performed strongly (97%), while active monitoring mechanism performed weakly (37%). In the administrative efficiency domain, both promptness of referral system (80%) and prompt arrival of funds (93%) performed well. At the individual level, providers with fewer enrolees encountered difficulties with reimbursement. Other factors significantly influenced each of the optimal-resource-use domains.

Conclusions
Fee-for-service payment method and claims review, in the provider payment and active monitoring mechanisms, respectively, performed weakly according to the providers’ (at individual-level) perspectives. A short-fall on the supply-side of health insurance could lead to a direct or indirect adverse effect on the demand-side of the scheme. Capitation payment per enrolees should be revised to conform to economic circumstances. Performance indicators and providers’ characteristics and experiences associated with resource use can assist policy makers to monitor and evaluate health insurance implementation.
Determinants of the citation rate of medical research publications from a developing country
Authors: Annalingam Anupama , Damayanthi Hasitha , Jayawardena Ranil , Ranasinghe Priyanga 
Published: March 2014

Abstract

Background
The number of citations received by an article is considered as an objective marker judging the importance and the quality of the research work. The present study aims to study the determinants of citations for research articles published by Sri Lankan authors.

Methods
Papers were selectively retrieved from the SciVerse Scopus® (Elsevier Properties S.A, USA) database for 10 years from 1st January 1997 to 31st December 2006, of which 50% were selected for inclusion by simple random sampling. The primary outcome measure was citation rate (defined as the number of citations during the 2 subsequent years after publication). Citation data was collected using the SciVerse Scopus® Citation Analyzer and self citations were excluded. A linear regression analysis was performed with ‘number of citations’ as the continuous dependent variable and other independent variables.

Result
The number of publications has steadily increased during the period of study. Over three quarter of papers were published in international journals. More than half of publications were research studies (55.3%), and most of the research studies were descriptive cross-sectional studies (27.1%). The mean number of citations within 2 years of publication was 1.7 and 52.1% of papers were not cited within the first two years of publication. The mean number of citations for collaborative studies (2.74) was significantly higher than that of non-collaborative studies (0.66). The mean number of citations did not significantly change depending on whether the publication had a positive result (2.08) or not (2.92) and was also not influenced by the presence (2.30) or absence (1.99) of the main study conclusion in the title of the article. In the linear regression model, the journal rank, number of authors, conducting the study abroad, being a research study or systematic review/meta-analysis and having regional and/or international collaboration all significantly increased the number of citations.

Conclusion
The journal rank, number of authors, conducting the study abroad, being a research study or systematic review/meta-analysis and having regional and/or international collaboration all significantly increased the number of citations. However, the presence of a positive result in the study did not influence the citation rate.
Achieving the Meaningful Use Standard: A Model for Implementing Change Within Medical Practices
Authors: Fryefield David C. , Staggs Stuart , Herman William , Stickler Alan , Ahmad Asif , Patt Debra A. , Beveridge Roy A. 
Published: March 2014

Purpose: Change management in medical practices is often an uphill battle. Lack of agreement on standards, ineffective leadership, inertia, inconsistent access to data, and inability to clearly define and communicate the benefits of change represent significant barriers to success. In 2009, the Health Information Technology for Economic and Clinical Health (HITECH) Act created the meaningful use (MU) incentive program administered through the Centers for Medicare and Medicaid Services (CMS). To earn financial incentive payments, eligible physicians adopt certified electronic health record (EHR) technology and use it to meet specified objectives. In response, leadership of the US Oncology Network launched an MU initiative designed to create a comprehensive system of tools, education, performance feedback, and support that would facilitate successful achievement of the MU standards. Methods: The EHR used by the majority of network physicians was modified according to the MU specifications, and EHR certification was obtained. Baseline compliance data were measured for each of the MU standards and for each of the eligible physicians. Physician and staff workflow processes necessary for consistent data input and compliance were outlined for each standard. Each practice identified one or more staff members who would act as MU leads. Training modules were developed for the MU leads as well as for physicians, mid-level providers, nurses, medical assistants, and office staff. An MU measurement tool was created, designed to target areas for MU process improvement and automate reporting. Data were updated and verified weekly to provide timely feedback to practices, including individual physician detail and links to individual patient records. Results: A total of 943 practitioners within the US Oncology Network met eligibility criteria for the MU program. At baseline, compliance with each MU standard ranged from 0% (clinical summaries) to 100% (computerized order entry). In many cases, data were simply not being entered into the EHR. Time from program launch to first submission of MU attestation was 18 months. As of March 2013, 781 practitioners (83%) had achieved the MU standards. In comparison, CMS reported that 44% of all eligible physicians and 26% of hematologists and oncologists had successfully achieved Medicare MU standards and received payment. Conclusion: Successful change management in medical practices can be accomplished through a comprehensive system of leadership, education, support, timely feedback of data, and clearly defined incentives. Incentives alone may be far less effective.
Genetically encoded molecular probes to visualize and perturb signaling dynamics in living biological systems
Authors: Sample Vedangi , Mehta Sohum , Zhang Jin 
Published: March 2014

ABSTRACTIn this Commentary, we discuss two sets of genetically encoded molecular tools that have significantly enhanced our ability to observe and manipulate complex biochemical processes in their native context and that have been essential in deepening our molecular understanding of how intracellular signaling networks function. In particular, genetically encoded biosensors are widely used to directly visualize signaling events in living cells, and we highlight several examples of basic biosensor designs that have enabled researchers to capture the spatial and temporal dynamics of numerous signaling molecules, including second messengers and signaling enzymes, with remarkable detail. Similarly, we discuss a number of genetically encoded biochemical perturbation techniques that are being used to manipulate the activity of various signaling molecules with far greater spatial and temporal selectivity than can be achieved using standard pharmacological or genetic techniques, focusing specifically on examples of chemically driven and light-inducible perturbation strategies. We then describe recent efforts to combine these diverse and powerful molecular tools into a unified platform that can be used to elucidate the molecular details of biological processes that may potentially extend well beyond the realm of signal transduction.
A Meniscus-climbing Gel Robot
Authors: Hara Yusuke , Saiki Mami , Suzuki Tomoya , Kikuchi Koki 
Published: March 2014

Abstract
We succeeded in the construction of a novel meniscus-climbing gel robot that autonomously converted the chemical energy from the Belousov–Zhabotinsky (BZ) reaction to mechanical work. The gel periodically bent in synchronization with the change in the redox state of the [Ru(bpy)2(vmbpy)] moiety, owing to an asymmetric structure in the gel. The climbing force of the gel robot originated from the change in the surface tension due to the periodic change in the shape of the gel. The maximum speed of the gel robot was 1.5 mm s−1.