bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melding a New 3-Dimensional Agarose Colony Assay with the Emax Model to Determine the Effects of Drug Combinations on Cancer Cells
Authors: Kajiwara Yoshinori , Panchabhai Sonali , Liu Diane D. , Kong Maiying , Lee J. Jack , Levin Victor A. 
Published: October 2014

The goal of our study was two-fold: (i) develop a robust 3D colony assay methodology to interrogate drug combinations using GelCount™ and (ii) to develop 2-drug combinations that might be useful in the clinic for the treatment of high-grade gliomas. We used three glioma cell lines (U251MG, SNB19, and LNZ308) and two adenocarcinoma cell lines (MiaPaCa and SW480) grown as colonies in a two-tiered agarose cultures. We evaluated two-drug combinations of difluoromethylornithine (DFMO), carboplatin, vorinostat (SAHA), and docetaxel. To analyze for antitumor efficacy we used GelCount™ to measure the area under the curve for tumor colony volumes (μm2 x OD) in each plate. The non-linear dose-response Emax model and the interaction index based on the Loewe additivity are applied to calculate two-drug synergy, additive, and antagonistic interactions. For glioblastoma cell lines, (i) carboplatin followed by DFMO was synergistic or additive in 2/3 cell lines, (ii) carboplatin before SAHA was synergistic in 1 cell line, (iii) carboplatin before docetaxel was synergistic in 2/3 cell lines and partially additive in the third, (iv) SAHA before docetaxel was synergistic in 1/3 cell lines, (v) docetaxel before DFMO was additive or partially active in 3/3 cell lines, and (vi) DFMO plus SAHA was inactive regardless of order. In the MiaPaCA cell line, synergy occurred when DFMO followed carboplatin and, at short exposure times, when SAHA was combined with carboplatin (regardless of order). In the SW480 cell line synergy occurred only in short exposures for carboplatin followed by docetaxel; additive and mixed partial effects were also seen with DFMO plus carboplatin or docetaxel (regardless of order), carboplatin before DFMO, carboplatin before SAHA, and docetaxel before carboplatin. In conclusion, by applying the Gelcount™ automated counting and sizing of colonies and the use of Emax and Loewe models to define drug interactions, we can reliably define drug combination efficacy as a function of log dose and duration of drug exposure.
Stereotactic Radiotherapy of the Liver: A Bridge to Transplantation
Authors: AlHamad AbdulAziz , Hassanain Mazen , Michel René P. , Metrakos Peter , Roberge David 
Published: October 2014

Patients with hepatocellular carcinoma (HCC) have limited curative therapeutic options. In North America, liver transplantation is one of the most commonly used curative therapies. Many potential transplant patients will be treated with another therapeutic modality to prevent local disease progression while awaiting organ donation. We present the case of 60-years old male diagnosed with HCC and awaiting liver transplantation. Prior to registration on the transplant list, the patient had a significant increase of his serum alpha-fetoprotein level. Due to his vascular anatomy and tumor location, he was not a candidate for more standard local ablative therapies. He was thus offered stereotactic radiotherapy as a bridge to liver transplantation. He received 50Gy in 5 fractions using respiratory gating. Following this, he had a complete radiological and serological response without worsening of his baseline Child-Pugh class C cirrhosis. Following transplant, 13 months later, pathological examination of the liver explant revealed only scarring at the site of radiation. This case illustrated the fact that hepatic stereotactic radiotherapy is a promising and safe treatment for patients with HCC. In selected patients, it can be a bridge to transplantation and, on its own, has the potential to induce complete pathological response in non-surgical candidates.
An X-ray Computed Tomography/Positron Emission Tomography System Designed Specifically for Breast Imaging
Authors: Boone John M. , Yang Kai , Burkett George W. , Packard Nathan J. , Huang Shih-ying , Bowen Spencer , Badawi Ramsey D. , Lindfors Karen K. 
Published: October 2014

Mammography has served the population of women who are at-risk for breast cancer well over the past 30 years. While mammography has undergone a number of changes as digital detector technology has advanced, other modalities such as computed tomography have experienced technological sophistication over this same time frame as well. The advent of large field of view flat panel detector systems enable the development of breast CT and several other niche CT applications, which rely on cone beam geometry. The breast, it turns out, is well suited to cone beam CT imaging because the lack of bones reduces artifacts, and the natural tapering of the breast anteriorly reduces the x-ray path lengths through the breast at large cone angle, reducing cone beam artifacts as well. We are in the process of designing a third prototype system which will enable the use of breast CT for image guided interventional procedures. This system will have several copies fabricated so that several breast CT scanners can be used in a multi-institutional clinical trial to better understand the role that this technology can bring to breast imaging.
Influence of iMRI-Guidance on the Extent of Resection and Survival of Patients with Glioblastoma Multiforme
Authors: Senft Christian , Franz Kea , Blasel Stella , Oszvald Ági , Rathert Julian , Seifert Volker , Gasser Thomas 
Published: October 2014

Intraoperative MRI (iMRI) is used in glioma surgery mainly to determine the extent of resection, allowing surgeons to immediately continue resection in case of residual tumor tissue. The aim of this study is to report on the influence of the use of iMRI on the extent of resection and survival of patients with glioblastoma multiforme (GBM). We analyzed our prospectively collected database of patients with GBM operated upon during the initial period after installation of an iMRI; between July 2004 and December 2005, all patients with GBM undergoing intended complete tumor resection were included in this study, while patients undergoing mere tumor biopsy or intended incomplete resection were not. In total, 43 Patients met the inclusion criteria. Of these, 10 patients (23.3%) were operated upon with the help of iMRI while 33 underwent conventional tumor resection. All patients underwent postoperative high-field MR imaging at 1.5 Tesla to determine the extent of resection. Subsequently, all patients received adjuvant treatment. Median patient age was 60.0 years; median overall survival was 70.7 weeks. Radiologically complete tumor resection (P < 0.001) and the administration of temozolomide chemotherapy (P < 0.01) were statistically significant prognostic factors in a multivariate analysis. The rate of complete tumor resections was significantly higher in the iMRI group than in the conventional surgery group (P < 0.05). Patient age was not a prognostic factor in our series of patients (P = 0.22). Intraoperative MRI is a helpful tool to increase the extent of resection in GBM surgery and thereby improve patient survival.
Hypofractionated Extracranial Stereotactic Radiotherapy Boost for Gynecologic Tumors: A Promising Alternative to High-Dose Rate Brachytherapy
Authors: Jorcano Sandra , Mollà Meritxell , Escudé Lluís , Sanz Sergi , Hidalgo Alberto , Toscas Jose Ignacio , Linero Dolors , Miralbell Raymond 
Published: October 2014

The purpose of this study is to report toxicity and outcome results in patients with gynaecological tumours treated with a final boost using extra-cranial stereotactic radiotherapy (SRT) with a linac-based micro-multileaf collimator technique as an alternative to high-dose rate brachytherapy (HDR-BT). Since January 2002, 26 patients with either endometrial (n = 17) or cervical (n = 9) cancer were treated according to this protocol: 45–50.4 Gy external radiotherapy (RT) to the pelvic ± para-aortic regions followed by a final SRT boost of 2 × 7 Gy to the vaginal vault (4–7 day interval between fractions). Median age was 62 years (37–74 range). Fifteen patients were diagnosed with adenocarcinoma, 7 with squamous-cell carcinoma, and 4 with sarcoma. FIGO stage I (n = 17), stage II (n = 7), and stage III (n = 2). Toxicity was scored according to RTOG/EORTC criteria. No severe (>grade-3) acute urinary or low-gastrointestinal (GI) toxicity was observed during treatment and up to 3 months after treatment completion. Moderate (grade ≤ 3) acute urinary or low-GI toxicity was observed in 23% and 35% of patients, respectively. After a median follow-up of 47 months (4–77, range), late urinary, low-GI, and sexual ≥grade-2 (worst score) has been reported in 4%, 12% and 29.4% of patients, respectively. The 3-year loco-regional failure-free and overall survival rates were 96% and 95%, respectively. Preliminary results on feasibility, tolerance, and outcome with SRT are encouraging and may be considered a sound alternative to HDR-BT for gynecologic tumors.
Toward Truly Optimal IMRT Dose Distribution: Inverse Planning with Voxel-specific Penalty
Authors: Lougovski Pavel , LeNoach Jordan , Zhu Lei , Ma Yunzhi , Censor Yair , Xing Lei 
Published: October 2014

Purpose: To establish an inverse planning framework with adjustable voxel penalty for more conformal IMRT dose distribution as well as improved interactive controllability over the regional dose distribution of the resultant plan. Materials and Method: In the proposed coarse-to-fine planning scheme, a conventional inverse planning with organ specific parameters is first performed. The voxel penalty scheme is then “switched on” by allowing the prescription dose to change on an individual voxel scale according to the deviation of the actual voxel dose from the ideally desired dose. The rationale here is intuitive: when the dose at a voxel does not meet its ideal dose, it simply implies that this voxel is not competitive enough when compared with the ones that have met their planning goal. In this case, increasing the penalty of the voxel by varying the prescription can boost its competitiveness and thus improve its dose. After the prescription adjustment, the plan is re-optimized. The dose adjustment/re-optimization procedure is repeated until the resultant dose distribution cannot be improved anymore. The prescription adjustment on a finer scale can be accomplished either automatically or manually. In the latter case, the regions/voxels where a dose improvement is needed are selected visually, unlike in the automatic case where the selection is done purely based on the difference of the actual dose at a given voxel and its ideal prescription. The performance of the proposed method is evaluated using a head and neck and a prostate case. Results: An inverse planning framework with the voxel-specific penalty is established. By adjusting voxel prescriptions iteratively to boost the region where large mismatch between the actual calculated and desired doses occurs, substantial improvements can be achieved in the final dose distribution. The proposed method is applied to a head and neck case and a prostate case. For the former case, a significant reduction in the maximum dose to the brainstem is achieved while the PTV dose coverage is greatly improved. The doses to other organs at risk are also reduced, ranging from 10% to 30%. For the prostate case, the use of the voxel penalty scheme also results in vast improvements to the final dose distribution. The PTV experiences improved dose uniformity and the mean dose to the rectum and bladder is reduced by as much as 15%. Conclusion: Introduction of the spatially non-uniform and adjustable prescription provides room for further improvements of currently achievable dose distributions and equips the planner with an effective tool to modify IMRT dose distributions interactively. The technique is easily implementable in any existing inverse planning platform, which should facilitate clinical IMRT planning process and, in future, off-line/on-line adaptive IMRT.
High prevalence of symptoms in a severely abused “non‐patient” women population
Authors: Pallotta N , Piacentino D , Ciccantelli B , Rivera M , Golini N , Spagnoli A , Vincoli G , Farchi S , Corazziari ES 
Published: October 2014

ObjectiveThe objective of this article is to assess the prevalence of somatic symptoms and of gastrointestinal (GI) syndromes in abused “non‐patient” women and the association with the time of perpetration, type, and severity of abuse.MethodsSixty‐seven women, 18–58 years, receiving shelter in anti‐violence associations were invited to fill out an anonymous questionnaire with a medical and an abuse section. The severity of abuse was expressed as the 0–6 Abuse Severity Measure (ASM). The association between abuse characteristics and the number of symptoms, and GI syndromes was assessed by Poisson regression model.ResultsMost women suffered from childhood and adulthood sexual and physical abuse. They reported a mean of 5.1 GI symptoms (range 0–13; median 5; IQR 6) and of 1.3 extra‐GI symptoms (range 0–6; median 1; IQR 2); 30% of women matched the Rome II Criteria for one, 36% for two, and 4.4% for three or more syndromes, respectively. Women with an ASM of 5–6, having suffered from both sexual and physical abuse, reported significantly (p  = 0.02) more GI symptoms, but not extra‐GI ones (p  = 0.07), and met criteria for more GI syndromes than women with an ASM ≤4 and those reporting only one type of abuse. No association was found between the time of perpetration of the abuse and the number of GI and extra‐GI symptoms.ConclusionsSymptoms in abused “non‐patient” women mainly concern the abdomen and the GI tract. A history of severe, combined physical and sexual abuse is associated with a higher number of GI symptoms.
How I treat polycythemia vera
Authors: Vannucchi Alessandro M. 
Published: October 2014

AbstractPolycythemia vera (PV) is a chronic myeloproliferative neoplasm associated with JAK2 mutations (V617F or exon 12) in almost all cases. The World Health Organization has defined the criteria for diagnosis, but it is still unclear which parameter (hemoglobin or hematocrit) is the most reliable for demonstrating increased red cell volume and for monitoring response to therapy; also, the role of bone marrow biopsy is being revisited. PV is associated with reduced survival because of cardiovascular complications and progression to post-PV myelofibrosis or leukemia. Criteria for risk-adapted treatment rely on the likelihood of thrombosis. Controlled trials have demonstrated that incidence of cardiovascular events is reduced by sustained control of hematocrit with phlebotomies (low-risk patients) and/or cytotoxic agents (high-risk patients) and antiplatelet therapy with aspirin. Hydroxyurea and interferon may be used as first-line treatments, whereas busulfan is reserved for patients that are refractory or resistant to first-line agents. However, there is no evidence that therapy improves survival, and the significance of reduction of JAK2 mutated allele burden produced by interferon is unknown. PV is also associated with a plethora of symptoms that are poorly controlled by conventional therapy. This article summarizes my approach to the management of PV in daily clinical practice.
Predictors of positive and negative parenting behaviours: evidence from the ALSPAC cohort
Authors: Thomson Rachel M , Allely Clare S , Purves David , Puckering Christine , McConnachie Alex , Johnson Paul CD , Golding Jean , Gillberg Christopher , Wilson Philip 
Published: October 2014

AbstractBackgroundThis study aimed to establish the predictors of positive and negative parenting behaviours in a United Kingdom population. The majority of previous research has focused on specific risk factors and has used a variety of outcome measures. This study used a single assessment of parenting behaviours and started with a wide range of potential pre- and post-natal variables; such an approach might be used to identify families who might benefit from parenting interventions.MethodsUsing a case-control subsample of 160 subjects from the Avon Longitudinal Study of Parents and Children (ALSPAC), regression analysis was undertaken to model parenting behaviours at 12 months as measured by the Mellow Parenting Observational System.ResultsPositive parenting increased with maternal age at delivery, levels of education and with prenatal anxiety. More negative interactions were observed among younger mothers, mothers with male infants, with prenatal non-smokers and among mothers who perceived they had a poor support structure.ConclusionsThis study indicates two factors which may be important in identifying families most at risk of negative parenting: younger maternal age at delivery and lack of social support during pregnancy. Such factors could be taken into account when planning provision of services such as parenting interventions. We also established that male children were significantly more likely to be negatively parented, a novel finding which may suggest an area for future research. However the findings have to be accepted cautiously and have to be replicated, as the measures used do not have established psychometric validity and reliability data.
Dietary elimination of children with food protein induced gastrointestinal allergy – micronutrient adequacy with and without a hypoallergenic formula?
Authors: Meyer Rosan , De Koker Claire , Dziubak Robert , Godwin Heather , Dominguez‐Ortega Gloria , Shah Neil 
Published: October 2014

AbstractBackgroundThe cornerstone for management of Food protein‐induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake.MethodA prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi‐quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS).ResultsOne‐hundred‐and‐five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 ‐ 67.7]. Fifty‐three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS.ConclusionThis study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies.
A radiographic and anthropometric study of the effect of a contoured sandal and foot orthosis on supporting the medial longitudinal arch
Authors: Escalona‐Marfil Carles , McPoil Thomas G , Mellor Rebecca , Vicenzino Bill 
Published: October 2014

AbstractBackgroundIn‐shoe foot orthoses improve conditions such as plantar heel pain (fasciitis), probably due to their ability to raise the medial longitudinal arch of the foot and lower the stress on the plantar tissues. Increasingly the arch‐profile form of the in‐shoe foot orthosis is being incorporated into sandal footwear, providing an alternative footwear option for those who require an orthosis. The purpose of this study was to evaluate if a sandal that incorporates the arch‐profile of an in‐shoe foot orthosis does indeed raise the medial longitudinal arch.MethodsThree commercially available non‐medical devices (contoured and flat sandal, prefabricated in‐shoe orthosis) worn by healthy individuals were studied in two independent experiments, one using radiographic measurements in Australia (n = 11, 6 female, age 26.1 ± 4.3 yrs, BMI 22.0 ± 2.4 kg/m2) and the other utilising anthropometric measures in the USA (n = 10, 6 female, age 26.3 ± 3.8 yrs, BMI 23.5 ± 3.7 kg/m2). A barefoot condition was also measured. Dorsal arch height was measured in both experiments, as well as in subtalar neutral in the anthropometric experiment. One way repeated measures ANOVA with follow up Bonferroni‐corrected pairwise comparisons were used to test differences between the conditions (contoured and flat sandal, orthosis, barefoot). Mean difference and 95% confidence intervals (CI) and standardised mean differences (SMD) were also calculated.ResultsThe contoured sandal significantly increased dorsal arch height compared to barefoot and flat sandal in both the anthropometric and radiographic experiments with SMD ranging from 0.95 (mean difference 5.1 mm (CI: 0.3, 1.6)) to 1.8 (4.3 mm (1.9, 6.6)). There were small differences between the contoured sandal and orthosis of 1.9 mm (0.6, 3.3) in the radiographic experiment and 1.2 mm (‐0.4, 0.9) in the anthropometric experiment. The contoured sandal approximated the subtalar neutral position (0.4 mm (‐0.5, 0.7)).ConclusionsMedial longitudinal arch height is elevated by contoured sandals and approximates subtalar joint neutral position of the foot and that achieved by an orthosis. Practitioners wanting to increase the medial longitudinal arch can do so with either an orthosis or a contoured sandal that includes the raised arch profile form of an orthosis.