bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer
Authors: Ciprotti Marika , Tebbutt Niall C. , Lee Fook-Thean , Lee Sze-Ting , Gan Hui K. , McKee David C. , O'Keefe Graeme J. , Gong Sylvia J. , Chong Geoffrey , Hopkins Wendie , Chappell Bridget , Scott Fiona E. , Brechbiel Martin W. , Tse Archie N. , Jansen Mendel , Matsumura Manabu , Kotsuma Masakatsu , Watanabe Rira , Venhaus Ralph , Beckman Robert A. , Greenberg Jonathan , Scott Andrew M. 
Published: June 2015

Purpose CS-1008 (tigatuzumab) is a humanized, monoclonal immunoglobulin G1 (IgG1) agonistic antibody to human death receptor 5. The purpose of this study was to investigate the impact of CS-1008 dose on the biodistribution, quantitative tumor uptake, and antitumor response in patients with metastatic colorectal cancer (mCRC). Patients and Methods Patients with mCRC who had received at least one course of chemotherapy were assigned to one of five dosage cohorts and infused with a weekly dose of CS-1008. Day 1 and day 36 doses were trace-labeled with indium-111 (111In), followed by whole-body planar and regional single-photon emission computed tomography (SPECT) imaging at several time points over the course of 10 days. Results Nineteen patients were enrolled. 111In-CS-1008 uptake in tumor was observed in only 12 patients (63%). 111In-CS-1008 uptake and pharmacokinetics were not affected by dose or repeated drug administration. 111In-CS-1008 biodistribution showed gradual blood-pool clearance and no abnormal uptake in normal tissue. No anti–CS-1008 antibody development was detected. One patient achieved partial response (3.7 months duration), eight patients had stable disease, and 10 patients had progressive disease. Clinical benefit rate (stable disease + partial response) in patients with 111In-CS-1008 uptake in tumor was 58% versus 28% in patients with no uptake. An analysis of individual lesions showed that lesions with antibody uptake were one third as likely to progress as those without antibody uptake (P = .07). Death-receptor–5 expression in archived tumor samples did not correlate with 111In-CS-1008 uptake (P = .5) or tumor response (P = .6). Conclusion Death-receptor–5 imaging with 111In-CS-1008 reveals interpatient and intrapatient heterogeneity of uptake in tumor, is not dose dependent, and is predictive of clinical benefit in the treatment of patients who have mCRC.
Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial
Authors: Sandmann Thomas , Bourgon Richard , Garcia Josep , Li Congfen , Cloughesy Timothy , Chinot Olivier L. , Wick Wolfgang , Nishikawa Ryo , Mason Warren , Henriksson Roger , Saran Frank , Lai Albert , Moore Nicola , Kharbanda Samir , Peale Franklin , Hegde Priti , Abrey Lauren E. , Phillips Heidi S. , Bais Carlos 
Published: June 2015

Purpose The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup. Patients and Methods A total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype. Results A multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only. Conclusion Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set.
Accountable Care Organizations and Population Health Organizations
Authors: Casalino Lawrence P. , Erb Natalie , Joshi Maulik S. , Shortell Stephen M. 
Published: June 2015

Abstract
Accountable care organizations (ACOs) and hospitals are investing in improving “population health,” by which they nearly always mean the health of the “population” of patients “attributed” by Medicare, Medicaid, or private health insurers to their organizations. But population health can and should also mean “the health of the entire population in a geographic area.” We present arguments for and against ACOs and hospitals investing in affecting the socioeconomic determinants of health to improve the health of the population in their geographic area, and we provide examples of ACOs and hospitals that are doing so in a limited way. These examples suggest that ACOs and hospitals can work with other organizations in their community to improve population health. We briefly present recent proposals for such coalitions and for how they could be financed to be sustainable.
Precision-cut kidney slices (PCKS) to study development of renal fibrosis and efficacy of drug targeting ex vivo
Authors: Poosti Fariba , Pham Bao Tung , Oosterhuis Dorenda , Poelstra Klaas , van Goor Harry , Olinga Peter , Hillebrands Jan-Luuk 
Published: June 2015

Renal fibrosis is a serious clinical problem forming the utmost cause of need for renal replacement therapy. No adequate preventive or curative therapy is available that can be clinically used to specifically target renal fibrosis. The search for new efficacious treatment strategies is therefore warranted. Although in vitro models using homogeneous cell populations have contributed to the understanding of the pathogenetic mechanisms involved in renal fibrosis, these models poorly mimic the complex in vivo milieu. Therefore, here we evaluated a precision-cut kidney slice (PCKS) model as a new, multicellular ex vivo model to study development of fibrosis and the prevention thereof using anti-fibrotic compounds.
Precision-cut slices (200-300 µm thickness) were prepared from healthy C57BL/6 mouse kidneys using a Krumdieck tissue slicer. To induce changes mimicking the fibrotic process, slices were incubated with TGFβ1 (5 ng/ml) for 48 hours in the presence or absence of the anti-fibrotic cytokine IFNγ (1 µg/ml) or an IFNγ conjugate which is targeted to the PDGFRβ (PPB-PEG-IFNγ). Following culture, tissue viability (ATP-content) and expression of α-SMA, fibronectin, collagen I, and collagen III were determined using real-time PCR and immunohistochemistry.
Slices remained viable up to 72 hours of incubation and no significant effects of TGFβ1 and IFNγ on viability were observed. TGFβ1 markedly increased α-SMA, fibronectin, and collagen I mRNA and protein expression levels. IFNγ and PPB-PEG-IFNγ significantly reduced TGFβ1-induced fibronectin, collagen I and collagen III mRNA expression which was confirmed by immunohistochemistry.
The PKCS model is a novel tool to test the pathophysiology of fibrosis and to screen the efficacy of anti-fibrotic drugs ex vivo in a multicellular and pro-fibrotic milieu. Major advantage of the slice model is that it can be used not only for animal but also for (fibrotic) human kidney tissue.
Typification and etymology of Aublet's Rubiaceae names
Authors: Delprete Piero G. 
Published: June 2015

AbstractThe ongoing Rubiaceae treatment for the Flora of the Guianas prompted a detailed study of the rubiaceous taxa described by Aublet (“Fusée Aublet”), one of the earliest botanists to collect in South America. This study led to the recognition that a publication by Lanjouw and Uittien in 1940 wherein the authors reported the discovery of an additional set of Aublet specimens in the Jean‐Jacques Rousseau herbarium (P‐JJR) also included many previously unrecognized typifications of Aublet names. This study presents the typifications of the 26 generic and 53 specific Rubiaceae epithets introduced by Aublet in his Histoire. The new combinations Coussarea lutea and Schradera scandens are also proposed.
A synopsis of Ipomoea (Convolvulaceae) in the Americas: Further corrections, changes, and additions
Authors: Austin Daniel F. , Staples George W. , Simão-Bianchini Rosangela 
Published: June 2015

AbstractContinuing studies of American Ipomoea have accounted for a large percentage of the unplaced names remaining in the 1996 publication by Austin and Huáman. To accomplish the current list we have studied protologues and examined type specimens or images of type specimens or other original material. In this paper we treat the binomials proposed before 1995 and add names published since that year. We include three categories: Accepted taxa, Additions and corrections to the 1996 and 1998 lists of unplaced names, and Unplaced names. In total, we here review 336 of the taxa published in American members of Ipomoea to bring their nomenclature and taxonomy to date. We have now reduced the unplaced names by about seventy percent.
A phylogeny and revised classification for the Apatesieae (Aizoaceae: Ruschioideae) with a comparison of centres of diversity
Authors: Klak Cornelia , Hanáček Pavel , Bruyns Peter V. 
Published: June 2015

AbstractThe Apatesieae (Aizoaceae) is a small tribe of 11 species in seven genera, Apatesia, Carpanthea, Caryotophora, Conicosia, Hymenogyne, Saphesia and Skiatophytum. All are succulent annual or perennial herbs with mostly flat, rarely trigonous to terete leaves. Analysis of molecular data from four plastid and nuclear ITS sequences confirm that the two informal groups identified earlier within the Apatesieae, the “Apatesia‐group” and the “Skiatophytum‐group”, as well as all genera were found to be monophyletic. The relationships among genera of the “Apatesia‐group”, however, differ from those previously suggested, which were largely based on characters of the fruits. Here we show that characters of the fruit are highly homoplasious. Our analysis of distributional data for the three major clades of the Aizoaceae with mesomorphic leaves, namely Apatesieae (Ruschioideae), Aizooideae and Mesembryanthemoideae, shows that each has different centres of diversity. The Apatesieae are most diverse in the south‐western Cape, in the fynbos of the Cape Floristic Region (CFR) and they are restricted to the Greater Cape Floristic Region (GCFR). We revise the classification for the Apatesieae and include the monotypic genera Caryotophora and Saphesia in Skiatophytum, in order to increase the phylogenetic information conveyed by the classification. We show that the lectotype and protologue of Mesembryanthemum flaccidum do not correspond to the species currently associated with this name, which we therefore describe as a new species, i.e., Skiatophytum flaccidifolium. In addition, we describe a new subspecies, Hymenogyne glabra subsp. namaquensis, which is endemic to the Kamieskroon area in Namaqualand. Amended descriptions for Skiatophytum and Hymenogyne as well as an improved key to the genera of the Apatesieae and to the species of Skiatophytum are provided.
Salvage of failed osteosynthesis of an intracapsular fracture of the femoral neck using two cannulated compression screws and a vascularised iliac crest bone graft
Authors: Xiaobing Y. , Dewei Z. 
Published: June 2015

We evaluated the outcome of treatment of nonunion of an intracapsular fracture of the femoral neck in young patients using two cannulated screws and a vascularised bone graft. A total of 32 patients (15 women and 17 men, with a mean age of 36.5 years; 20 to 50) with failed internal fixation of an intracapsular fracture were included in the study. Following removal of the primary fixation, two cannulated compression screws were inserted with a vascularised iliac crest bone graft based on the ascending branch of the lateral femoral circumflex artery. At a mean follow-up of 6.8 years (4 to 10), union was achieved in 27 hips (84%). A total of five patients with a mean age of 40.5 years (35 to 50) had a persistent nonunion and underwent total hip arthroplasty as also did two patients whose fracture united but who developed osteonecrosis of the femoral head two years post-operatively. Statistical analysis showed that younger patients achieved earlier and more reliable union (p < 0.001). The functional outcome, as assessed by the Harris Hip score, was better in patients aged < 45 years compared with those aged > 45 years (p < 0.001). These findings suggest that further fixation using two cannulated compression screws and a vascularised iliac crest bone graft is an effective salvage treatment in patients aged < 45 years, in whom osteosynthesis of a displaced intracapsular fractures of the femoral neck has failed. Cite this article: Bone Joint J 2015; 97-B:988–91.
Particle characterisation and cytokine expression in failed small-diameter metal-on-metal total hip arthroplasties
Authors: Singh G. , Nuechtern J. V. , Meyer H. , Fiedler G. M. , Awiszus F. , Junk-Jantsch S. , Bruegel M. , Pflueger G. , Lohmann C. H. 
Published: June 2015

The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the ‘biologically active area’ of all metal wear particles may predict the type of peri-prosthetic tissue response. Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6). The overall distribution of the size and area of the particles in both lymphocyte and non-lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles. 14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß), and growth factors (granulocyte macrophage colony stimulating factor (GM-CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group. Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri-prosthetic response compared with those without this response. These results suggest that the ‘biologically active area’ predicts the type of peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA. Cite this article: Bone Joint J 2015;97-B:917–23.
Five-year comparison of wear using oxidised zirconium and cobalt–chrome femoral heads in total hip arthroplasty
Authors: Jassim S. S. , Patel S. , Wardle N. , Tahmassebi J. , Middleton R. , Shardlow D. L. , Stephen A. , Hutchinson J. , Haddad F. S. 
Published: June 2015

Oxidised zirconium (OxZi) has been developed as an alternative bearing surface for femoral heads in total hip arthroplasty (THA). This study has investigated polyethylene wear, functional outcomes and complications, comparing OxZi and cobalt–chrome (CoCr) as part of a three-arm, multicentre randomised controlled trial. Patients undergoing THA from four institutions were prospectively randomised into three groups. Group A received a CoCr femoral head and highly cross-linked polyethylene (XLPE) liner; Group B received an OxZi femoral head and XLPE liner; Group C received an OxZi femoral head and ultra-high molecular weight polyethylene (UHMWPE) liner. At five years, 368 patients had no statistically significant differences in short-form-36 (p = 0.176 mental, p = 0.756 physical), Western Ontario and McMaster Universities Osteoarthritis Index (p = 0.847), pain scores (p = 0.458) or complications. The mean rate of linear wear was 0.028 mm/year (standard deviation (sd) 0.010) for Group A, 0.023 mm/year (sd 0.010) for Group B, and 0.09 mm/year (sd 0.045) for Group C. Penetration was significantly higher in the UHMWPE liner group compared with both XLPE liner groups (p < 0.001) but no significant difference was noted between CoCr and OxZi when articulating with XLPE (p = 0.153). In this, the largest randomised study of this bearing surface, it appears that using a XLPE acetabular liner is more important in reducing THA component wear than the choice of femoral head bearing, at mid-term follow-up. There is a non-significant trend towards lower wear, coupling OxZi rather than CoCr with XLPE but long-term analysis is required to see if this observation changes with time and becomes significant. Cite this article: Bone Joint J 2015;97-B:883–9.
Reverse shoulder arthroplasty as a salvage procedure after failed internal fixation of fractures of the proximal humerus
Authors: Hussey M. M. , Hussey S. E. , Mighell M. A. 
Published: June 2015

Failed internal fixation of a fracture of the proximal humerus produces many challenges with limited surgical options. The aim of this study was to evaluate the clinical outcomes after the use of a reverse shoulder arthroplasty under these circumstances. Between 2007 and 2012, 19 patients (15 women and four men, mean age 66 years; 52 to 82) with failed internal fixation after a proximal humeral fracture, underwent implant removal and reverse shoulder arthroplasty (RSA). The mean follow-up was 36 months (25 to 60). The mean American Shoulder and Elbow Score improved from 27.8 to 50.1 (p = 0.019). The mean Simple Shoulder Test score improved from 0.7 to 3.2 (p = 0.020), and the mean visual analogue scale for pain improved from 6.8 to 4.3 (p = 0.012). Mean forward flexion improved from 58.7° to 101.1° (p < 0.001), mean abduction from 58.7° to 89.1° (p = 0.012), mean external rotation from 10.7° to 23.1° (p = 0.043) and mean internal rotation from buttocks to L4 (p = 0.034). A major complication was recorded in five patients (26%) (one intra-operative fracture, loosening of the humeral component in two and two peri-prosthetic fractures). A total of 15 patients (79%) rated their outcome as excellent or good, one (5%) as satisfactory, and three (16%) as unsatisfactory. An improvement in outcomes and pain can be expected when performing a RSA as a salvage procedure after failed internal fixation of a fracture of the proximal humerus. Patients should be cautioned about the possibility for major complications following this technically demanding procedure. Cite this article: Bone Joint J 2015;97-B:967–72.
Osteoarthritis of the hip in fibrous dysplasia of the proximal femur
Authors: Kim H-S. , Im S. B. , Han I. 
Published: June 2015

Deformity of the proximal femur in fibrous dysplasia leads to deviation of the mechanical axis of the hip, which may lead to the development of secondary osteoarthritis (OA). This study investigated the prevalence and predisposing factors for the development of OA in patients with fibrous dysplasia of the proximal femur. We reviewed the records of 209 patients from our institutional database with fibrous dysplasia of the proximal femur, investigating possible predisposing factors including patient demographics, the extent of the coxa vara deformity, the presence of peri-articular disease, and the overall burden of skeletal disease. Of the 209 patients, 24 (12%) had radiological evidence of OA in the ipsilateral hip. The prevalence was significantly higher in patients with polyostotic fibrous dysplasia compared with those with monostotic disease (p < 0.001). In a subgroup analysis of patients with polyostotic disease, the extent of deformity (quantified using the neck–shaft angle), and the presence of peri-articular disease (whether in the head of the femur or the acetabulum) were significant predictors of osteoarthritis (neck–shaft angle likelihood ratio (LR) = 0.847 per 1° increase, p = 0.004; presence of lesion in the head of the femur LR = 9.947, p = 0.027; presence of lesion in the acetabulum LR = 11.231, p = 0.014). Our data suggest that patients with polyostotic fibrous dysplasia have a high risk of developing secondary OA of the hips. This risk is higher in patients with peri-articular disease, and those with a more severe deformity of proximal femur. Cite this article: Bone Joint J 2015;97-B:1007–11.
Population genetic structure in medicinal plant Lallemantia iberica (Lamiaceae)
Authors: KOOHDAR FAHIMEH , SHEIDAI MASOUD , TALEBI SEYYED MEHDI , NOORMOHAMMADI ZAHRA 
Published: June 2015

Koohdar F, Sheidai M, Talebi SM, Noormohammadi Z. 2015. Population genetic structure in medicinal plant Lallemantia iberica (Lamiaceae). Biodiversitas 16: 139-144. Lallemantia iberica (Bieb.) Fischer and C.A. Meyer (sin. Dracocephalum ibericumM.Bieb.) also named Dragon's headâ€ is an annual plant cultivated for its seeds that contain about 30% -38% drying oil (siccative oil). Itsseed oil is used in foods, dye and varnish industry. L. iberica seeds have traditional uses as reconstitute, stimulant, diuretic andexpectorant. L. iberica in an important medicinal plant in our country and grows in various regions with different environmentalconditions. At present no investigation has been reported about population genetic structure of this valuable plant species in Iran.Therefore, we carried out population genetic analysis of 11 populations of L. iberica by using ISSR molecular markers for the first time.Genetic diversity analysis revealed high within population genetic variability. AMOVA test produced significant genetic differenceamong the studied populations. Mantel test revealed significant correlation between genetic distance and geographical distance of thepopulations. STRUCTURE analysis and K-Means clustering revealed population genetic fragmentation and the presence of three genepools for this species. The assignment test revealed the occurrence of limited gene flow among the populations. The results suggestedthat genetic divergence, limited gene flow, genetic drift and local adaptation have played role in diversification of L. iberica.
Key words: Gene flow, population fragmentation, IBD, Lallemantia iberica.