bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signal Transducers and Activators of Transcription: Novel Targets for Anticancer Therapeutics
Authors: Bowman Tammy , Yu Hua , Sebti Saïd , Dalton William , Jove Richard 
Published: August 2017

Background Through specific activation of gene expression, the family of proteins known as signal transducers and activators of transcription (STATs) converts extracellular stimuli into diverse biological responses. Beyond the normal signaling functions of STATs, recent evidence indicates that aberrant activation of STATs contributes to neoplastic transformation. Methods Current literature pertaining to the role of STAT proteins in oncogenesis is presented. Also, the rationale for developing novel approaches to disrupt STAT signaling is discussed, and the potential of STATs as anticancer targets in treating human cancer is reviewed. Results The discovery that certain oncoproteins constitutively activate specific STATs, coupled with observations that elevated STAT activity occurs frequently in a spectrum of human tumors, establishes a direct link between STAT activation and neoplastic transformation. Significantly, abrogation of STAT signaling blocks oncogenesis in model in vitro and in vivo systems. These results make STATs attractive targets for rational design of small molecule inhibitors and gene therapy approaches to disrupt STAT signaling. Conclusions As a result of genetic, biochemical, and crystallographic analyses, the functional domains of STAT proteins have been well characterized. Based on these data, selective inhibitors of STAT function can be designed. Because disrupting STAT signaling has proven effective in blocking neoplastic transformation, it is proposed that STAT proteins represent promising targets for development of novel molecular therapeutics to treat human cancer.
Review of Three New Agents that Target Angiogenesis, Matrix Metalloproteinases, and Cyclin-Dependent Kinases
Authors: Lush Richard M. , Rudek Michelle A. , Figg William D. 
Published: August 2017

Background Many potential new antineoplastic agents are currently in various stages of clinical development. Three areas of drug development include antiangiogenic compounds, agents that inhibit matrix metalloproteinases, and agents that modulate cyclin-dependent kinases. Methods The authors reviewed the available data for endostatin, COL-3, and flavopiridol, each of which is being developed with one of the above-mentioned proposed mechanisms of action. These agents are among the first drugs to reach clinical testing that is focusing on these novel targets. Results Endostatin has finished preclinical testing and the first human trials are about to be initiated. COL-3 is in phase I testing in several locations. Phase I studies for flavopiridol have been completed and several phase II studies are underway. It is unknown at this point if any of these agents will provide clinical benefit to patients at doses that do not cause unacceptable toxicity. Conclusions These agents are currently at various stages of clinical testing. Albeit promising as potential modulators in molecular and biochemical pathways, continued research is needed into the toxicities and clinical usefulness of these agents.
Current Status of Partial Nephrectomy in the Management of Kidney Cancer
Authors: Van Ophoven Arndt , Tsui Ke-Hung , Shvarts Oleg , Laifer-Narin Sherelle , Belldegrun Arie S. 
Published: August 2017

Background The technique of partial nephrectomy for managing renal cancers is well recognized, but guidelines regarding indications for its use are not generally accepted. Methods The authors review the indications for partial nephrectomy in various clinical situations, and they include their own experience to clarify the utility of the technique. Results Intraoperative renal ultrasound and helical computed tomography can assist the surgeon in technical decisions. Partial nephrectomy is considered when nephrectomy would render the patient anephric and dependent on dialysis. Conclusions The technical and operative advances in partial nephrectomy make the approach increasingly attractive for patients with kidney cancer in a variety of clinical circumstances.
The Mainz Classification of Renal Cell Tumors
Authors: Diaz José I. , Mora Linda B. , Hakam Ardeshir 
Published: August 2017

Background Tumors arising from the renal tubular epithelium have variable characteristics and have been subject to a variety of histologic classifications. Methods The authors describe the distinct clinical, pathologic, phenotypic, and genotypic features of different types of renal tumors. Results The Mainz classification is now widely accepted because characteristic genetic alterations have been demonstrated in each tumor type. Conclusions The increasing emphasis on utilizing genetic characteristics of specific tumors is reflected by the more widespread use of the Mainz classification for renal cell tumors.
Theory-Based Evaluation Meets Ambiguity
Authors: Dahler-Larsen Peter 
Published: August 2017

As theory-based evaluation (TBE) engages in situations where multiple stakeholders help develop complex program theory about dynamic phenomena in politically contested settings, it becomes difficult to develop and use program theory without ambiguity. The purpose of this article is to explore ambiguity as a fruitful perspective that helps TBE face current challenges. Literatures in organization theory and political theory are consulted in order to cultivate the concept of ambiguity. Janus variables (which work in two ways) and other ambiguous aspects of program theories are classified and exemplified. Stances towards ambiguity are considered, as are concrete steps that TBE evaluators can take to identify and deal with ambiguity in TBE.
Imaging in paediatric spinal injury
Authors: Cassar-Pullicino Victor N , Leone Antonio 
Published: August 2017

Background Paediatric spinal injury is rare and exhibits many unique features. Attending clinicians and radiologists often lack knowledge, expertise and experience in dealing with a potential injury to the paediatric spine. Within the paediatric age range itself there are different age-dependent mechanisms that can injure the paediatric spine. Moreover, the anatomical features and degree of osseous maturity of the developing paediatric spine determine the biomechanical characteristics which promote unique patterns of spinal injury in each paediatric age group. Methods An expert illustrated narrative review of the literature. Results Multiple factors make the imaging interpretation of the injured paediatric spine challenging. Each imaging modality has strengths and weaknesses in depicting spinal anatomy which vary with the type of spinal injury and age of the paediatric patient. Conclusions Attending doctors need to be familiar with the imaging appearances of the normal paediatric spine, its normal variants as well as the imaging features characteristics of paediatric spinal injury seen on radiographs, computed tomography and magnetic resonance imaging.
Prevalence of cold sensitivity in upper extremity nerve compression syndromes
Authors: Wendt Michael , Novak Christine B. , Anastakis Dimitri J. 
Published: August 2017

This prospective observational study assessed the prevalence of cold sensitivity in patients with nerve compression using the Cold Intolerance Symptom Severity (CISS) questionnaire. One hundred patients (72 women, 28 men; mean age 59 years) with carpal tunnel syndrome ( n = 95) or cubital tunnel syndrome ( n = 5) were studied. Fifty-two patients reported symptoms of cold sensitivity with a mean CISS score of 50. Overall, significantly more women (58% vs. 36%) reported cold sensitivity with significantly worse CISS scores than men. Level of evidence: IV
The fulcrum axis: an accurate measure of glenoid version on radiographs and computed tomography
Authors: Mutch Jennifer , Sidler Martin , Sidler-Maier Claudia , Axelrod Terry , Nam Diane 
Published: August 2017

Background Proper glenoid position in total shoulder arthroplasty (TSA) is important. However, traditional glenoid version (GV) measurements overestimate retroversion on radiographs (XR) and computed tomography (CT). The fulcrum axis (FA) uses palpable surface landmarks and may be useful as an intra-operative guide. Also, the FA has not yet been validated on XR or CT in an arthritic population. Methods Four observers measured FA and GV on the XR, CT and three-dimensional CT (3DCT) of 40 patients who underwent TSA at a single institution from 2009 to 2015. Reliability and accuracy of FA and GV were calculated for XR and CT, using 3DCT as the gold standard. Results The mean FA and GV were 7.768° and 18.910° on XR; 6.23° and 12.920° on CT; and 8.100° and 7.740° on 3DCT, respectively. FA and GV were significantly different for XR and CT ( p < 0.001) but not for 3DCT ( p = 0.725). The inter-rater reliability, intra-rater reliability and accuracy of FA were not significantly different from GV and were 0.929 to 0.948, 0.779 to 0.974 and 0.674 to 0.705, respectively. However, the absolute difference of FA was closer to the gold standard (3DCT) than GV for XR (0.330° versus 11.172°) and CT (1.871° versus 5.178°) ( p < 0.001). Conclusions FA showed comparable reliability and accuracy to GV. However, FA more accurately reflected the gold standard.
Transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil versus transarterial chemoembolization using doxorubicin for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective analysis
Authors: Lee Sung Won , Lee Hae Lim , Han Nam Ik , Kwon Jung Hyun , Nam Soon Woo , Jang Jeong Won , Bae Si Hyun , Choi Jong Young , Yoon Seung Kew 
Published: August 2017

Background: More than one-third of hepatocellular carcinoma (HCC) patients are diagnosed at advanced stage with portal vein tumor thrombosis (PVTT) or extrahepatic metastasis. However, the outcomes of current therapeutic approaches are unsatisfactory. As a novel therapeutic strategy for unresectable HCC with PVTT, we analyzed the outcomes of transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil (TAC-ECF) and compared its therapeutic effects and toxicity with transarterial chemoembolization (TACE) using doxorubicin (DOX). Methods: A total of 540 consecutive HCC patients who received TACE at the Catholic Medical Center between January 2007 and November 2013 were enrolled. Of these patients, we retrospectively analyzed 129 Barcelona clinic liver cancer stage C HCC patients with PVTT who received either TAC-ECF or TACE using DOX. Results: The objective tumor response rate was higher in the TAC-ECF group, with 31.3% objective response rate after TAC-ECF compared to 10% after DOX treatment ( p = 0.004). Median follow-up period was 7 months (range, 1–57 months). The overall survival rate was also significantly higher in the TAC-ECF group compared to the DOX group (median 9.3 versus 4.6 months, p < 0.0001). Multivariate analysis revealed that TAC-ECF and extrahepatic metastasis were independent predictive factors for overall survival ( p < 0.0001 and p = 0.002 respectively). No serious adverse effects developed in both groups. Conclusions: TAC-ECF therapy was tolerable and showed higher overall survival rate and tumor response compared to the conventional TACE DOX in advanced stage HCC patients with PVTT. Therefore, TAC-ECF may be considered as an effective treatment option for patients with unresectable HCC.
Efficacy of oral contrast agents for upper gastrointestinal signal suppression in MRCP: A systematic review of the literature
Authors: Frisch Anne , Walter Thula C , Hamm Bernd , Denecke Timm 
Published: August 2017

Background Orally administered substances which suppress signals from gastrointestinal fluid can be used to enhance image quality in magnetic resonance cholangiopancreatography (MRCP). In daily practice, the available substances range from commercial products to regular viands such as fruit juices. Purpose To provide an overview on the significance of and the substances used as gastrointestinal fluid signal suppressors in MRCP. Material and Methods A systematic review of the existing literature was performed to evaluate the efficacy and efficiency of oral T2-signal suppressors in MRCP. Results Twenty-five publications on 16 different oral contrast media were identified. The most commonly used substances were ferumoxsil, ferric ammonium citrate, and pineapple juice. Twenty-three out of 25 publications supported the use of oral signal suppressors in MRCP. Advantages of oral signal suppressors include improved visualization of the pancreatobiliary ductal system, increased help with differential diagnoses, and higher detection rates of relevant diagnoses due to a reduction of overlaying signals. Conclusion The application of oral substances for gastrointestinal signal suppression in MRCP is recommendable. A variety of substances are used in daily routine with good but varying effectivity and patient tolerance.
Efficacy of a computed tomography-based navigation system for placement of the acetabular component in total hip arthroplasty for developmental dysplasia of the hip
Authors: Tsutsui Takahiko , Goto Tomohiro , Wada Keizo , Takasago Tomoya , Hamada Daisuke , Sairyo Koichi 
Published: August 2017

Purpose: Developmental dysplasia of the hip (DDH) presents a considerable surgical challenge in total hip arthroplasty (THA). Although the usefulness of computed tomography (CT)-based navigation in cup alignment has been reported, few reports have evaluated three-dimensional (3-D) cup positioning against the acetabulum specifically in patients with DDH. The purpose of this study was to evaluate the efficacy of a CT-based navigation system for alignment and spatial positioning of the cup in THA for patients with DDH. Methods: We reviewed 174 DDH THA cases in which CT-based navigation was used, and 75 cases in which a mechanical guide was used as a control group. Postoperative cup alignment and spatial positioning were evaluated by superimposition of a 3-D cup template onto the actual implanted cup using postoperative CT images, with pelvic coordinates matching the preoperative planning. Results: The proportion within the combined target zone (inclination and anteversion) was 97.7% in the navigation group and 61.3% in the non-navigation group. The mean absolute error between the intraoperative record and the postoperative measurement was 1.5° ± 1.3° for inclination and 2.1° ± 1.8° for anteversion in the navigation group. For acetabular cup positioning, the mean discrepancy between the preoperative planning and the postoperative measurements was 1.9 ± 1.6 mm on the transverse axis, 2.8 ± 2.3 mm on the longitudinal axis, and 1.7 ± 1.3 mm on the sagittal axis. Conclusion: THA using a CT-based navigation system achieved quite high accuracy of cup alignment angles and spatial cup positioning in primary THA for patients with DDH.
An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD
Authors: Poe Jonathan C. , Jia Wei , Su Hsuan , Anand Sarah , Rose Jeremy J. , Tata Prasanthi V. , Suthers Amy N. , Jones Corbin D. , Kuan Pei Fen , Vincent Benjamin G. , Serody Jonathan S. , Horwitz Mitchell E. , Ho Vincent T. , Pavletic Steven Z. , Hakim Frances T. , Owzar Kouros , Zhang Dadong , Blazar Bruce R. , Siebel Christian W. , Chao Nelson J. , Maillard Ivan , Sarantopoulos Stefanie 
Published: August 2017

Key PointsNOTCH2 activation confers a marked increase in BCR responsiveness by cGVHD patient B cells that associates with increased BLNK. ATRA increases the IRF4-to-IRF8 ratio and blocks aberrant NOTCH2-BCR activation without affecting cGVHD patient B-cell viability/function.
Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approach to HIV prevention
Authors: Lajoie Julie , Mwangi Lucy , Fowke Keith R. 
Published: August 2017

AbstractFor over three decades, HIV infection has had a tremendous impact on the lives of individuals and public health. Microbicides and vaccines studies have shown that immune activation at the genital tract is a risk factor for HIV infection. Furthermore, lower level of immune activation, or what we call immune quiescence, has been associated with a lower risk of HIV acquisition. This unique phenotype is observed in highly-exposed seronegative individuals from different populations including female sex workers from the Pumwani cohort in Nairobi, Kenya. Here, we review the link between immune activation and susceptibility to HIV infection. We also describe a new concept in prevention where, instead of targeting the virus, we modulate the host immune system to resist HIV infection. Mimicking the immune quiescence phenotype might become a new strategy in the toolbox of biomedical methods to prevent HIV infection.Clinical trial registration on clinicaltrial.gov: #NCT02079077
The action of herbal medicine on the libido: aspects of nutritional intervention in increasing sexual desire
Authors: da Cruz Amanda Cássia , Guerra Natália Gonçalves , de Souza Kerolayne Esper Barão Pacelhe , de Castro Eleutério Izabella , da Silva Leidhaiane Custódia , Otoni Elaine Gomes , Alves Michelle Rosa Andrade , Regis Wiliam César Bento 
Published: August 2017

Abstract
Introduction
The libido is considered to be a sexual drive in individuals that can be determined and influenced by several factors, such as social, psychological, and hormonal factors. It is known that nutritional aspects are important hormone regulators and that sexual dysfunction may, in many cases, be reversed with simple lifestyle changes.

Aims
The aim of the study is to describe the actions of herbal medicine on the libido with an appropriate level of scientific evidence.

Methodology
A systematic review of the PUBMED, Scielo, and EMBASE databases was conducted, using the keywords “libido, food, and nutrient.”

Results
This study identified 2798 articles, 34 of which were selected, as they discussed exclusive studies involving herbal medicine. Some herbal medicines stood out, including Tribulus terrestris, used to increase testosterone serum levels; Eurycoma longifólia, which, in addition to the increased testosterone serum levels, also leads to an increased biosynthesis of several androgens; ginseng, which increases energy levels and stimulates smooth muscle relaxation with nitrous oxide; Maca (Lepidium meyenii), which improves sexual performance, in addition to having androgenic effects; and Mondia whitei (ginger), which improves the libido and erection. In addition to these, one study has demonstrated the effective impact of a hypocaloric, hyperproteic, and hypolipidemic diet on the libido, both improving sexual and erectile functions and increasing testosterone levels.

Conclusion
Herbal medicine analyzed in this study demonstrate positive effects on the libido, thus proving that, along with nutritional intervention, it is also a promising field in nutrition actions that provide support to combat sexual dysfunctions.
Toward Electronic Surveillance of Invasive Mold Diseases in Hematology-Oncology Patients: An Expert System Combining Natural Language Processing of Chest Computed Tomography Reports, Microbiology, and Antifungal Drug Data
Authors: Ananda-Rajah Michelle R. , Bergmeir Christoph , Petitjean François , Slavin Monica A. , Thursky Karin A. , Webb Geoffrey I. 
Published: August 2017

Purpose Prospective epidemiologic surveillance of invasive mold disease (IMD) in hematology patients is hampered by the absence of a reliable laboratory prompt. This study develops an expert system for electronic surveillance of IMD that combines probabilities using natural language processing (NLP) of computed tomography (CT) reports with microbiology and antifungal drug data to improve prediction of IMD. Methods Microbiology indicators and antifungal drug–dispensing data were extracted from hospital information systems at three tertiary hospitals for 123 hematology-oncology patients. Of this group, 64 case patients had 26 probable/proven IMD according to international definitions, and 59 patients were uninfected controls. Derived probabilities from NLP combined with medical expertise identified patients at high likelihood of IMD, with remaining patients processed by a machine-learning classifier trained on all available features. Results Compared with the baseline text classifier, the expert system that incorporated the best performing algorithm (naïve Bayes) improved specificity from 50.8% (95% CI, 37.5% to 64.1%) to 74.6% (95% CI, 61.6% to 85.0%), reducing false positives by 48% from 29 to 15; improved sensitivity slightly from 96.9% (95% CI, 89.2% to 99.6%) to 98.4% (95% CI, 91.6% to 100%); and improved receiver operating characteristic area from 73.9% (95% CI, 67.1% to 80.6%) to 92.8% (95% CI, 88% to 97.5%). Conclusion An expert system that uses multiple sources of data (CT reports, microbiology, antifungal drug dispensing) is a promising approach to continuous prospective surveillance of IMD in the hospital, and demonstrates reduced false notifications (positives) compared with NLP of CT reports alone. Our expert system could provide decision support for IMD surveillance, which is critical to antifungal stewardship and improving supportive care in cancer.
The Role of Sequential BMP Signaling in Directing Human Embryonic Stem Cells to Bipotential Gonadal Cells
Authors: Sepponen Kirsi , Lundin Karolina , Knuus Katri , Väyrynen Pia , Raivio Taneli , Tapanainen Juha S , Tuuri Timo 
Published: August 2017

AbstractContextHuman gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but because of a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed.ObjectiveTo establish an in vitro method for studying differentiation of bipotential gonadal progenitors by using human embryonic stem cells (hESCs) and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation.DesignWe tested 17 protocols using activin A, CHIR-99021, and varying durations of BMP-7 and the BMP inhibitor dorsomorphin. Activation of activin A, WNT, and BMP pathways was optimized to induce differentiation.SettingAcademic research laboratory.Main Outcomes MeasuresCell differentiation, gene expression, and flow cytometry.ResultsThe two most efficient protocols consistently upregulated IM markers LHX1, PAX2, and OSR1 at days 2 to 4 and bipotential gonadal markers EMX2, GATA4, WT1, and LHX9 at day 8 of culture. The outcome depended on the combination of the duration, concentration, and type of BMP activation and the length of WNT signaling. Adjusting any of the parameters substantially affected the requirements for other parameters.ConclusionsWe have established a reproducible protocol for directed differentiation of hESCs into bipotential gonadal cells. The protocol can be used to model early gonadal development in humans and allows further differentiation to mature gonadal somatic cells.