bluuebunny/crossref_metadata_2025_split huggingface dataset:
A HER 1-2 Punch: Dual EGFR Targeting Deals Resistance a Deadly Blow
Authors: Gibbons Don L. , Byers Lauren Averett 
Published: September 2014

Abstract
Summary: Ten years after the approval of erlotinib, EGFR inhibitor resistance remains a major clinical challenge. The translation of afatinib plus cetuximab into the clinic provides a promising new option for the treatment of patients with EGFR-mutated lung cancer. Cancer Discov; 4(9); 991–4. ©2014 AACR.
See related article by Janjigian et al., p. 1036
Combining Radiation and Immunotherapy: A New Systemic Therapy for Solid Tumors?
Authors: Tang Chad , Wang Xiaohong , Soh Hendrick , Seyedin Steven , Cortez Maria Angelica , Krishnan Sunil , Massarelli Erminia , Hong David , Naing Aung , Diab Adi , Gomez Daniel , Ye Huiping , Heymach John , Komaki Ristuko , Allison James P. , Sharma Padmanee , Welsh James W. 
Published: September 2014

AbstractWith the recent success of checkpoint inhibitors and other immunomodulating agents, there has been renewed interest in the combination of such agents with radiation. The biologic premise behind such a strategy is that the tumor-antigen release achieved by localized radiation will promote specific tumor targeting by the adaptive immune system, which can be augmented further by systemic immune-stimulating agents. In this manner, clinicians hope to induce a phenomenon known as the abscopal effect, whereby localized radiation results in immune-mediated tumor regression in disease sites well outside of the radiation field. Herein, we present a comprehensive overview of the early clinical and preclinical evidence behind this approach. Cancer Immunol Res; 2(9); 831–8. ©2014 AACR.
Fibrinogen and factor XIII at the intersection of coagulation, fibrinolysis and inflammation
Authors: Hoppe Berthold 
Published: September 2014

SummaryFibrinogen and factor XIII are two essential proteins that are involved directly in fibrin gel formation as the final step of a sequence of reactions triggered by a procoagulant stimulus. Haemostasis is the most obvious function of the resulting fibrin clot. Different variables affect the conversion of fibrinogen to fibrin as well as the mode of fibrin polymerisation and fibrin crosslinking, hereby, critically influencing the architecture of the resulting fibrin network and consequently determining its mechanical strength and resistance against fibrinolysis. Due to fibrinogen’s structure with a multitude of domains and binding motifs the fibrin gel allows for complex interactions with other coagulation factors, with profibrinolytic as well as antifibrinolyic proteins, with complement factors and with various cellular receptors. These interactions enable the fibrin network to control its own further state (i. e. expansion or degradation), to influence innate immunity, and to function as a scaffold for cell migration processes. During the whole process of fibrin gel formation biologically active peptides and protein fragments are released that additionally influence cellular processes via chemotaxis or by modulating cell-cell interactions. Thus, it is not surprising that fibrinogen and factor XIII in addition to their haemostatic function influence innate immunity as well as cell-mediated reactions like wound healing, response to tissue injury or inflammatory processes. The present review summarises current knowledge of fibrinogen’s and factor XIII’s function in coagulation and fibrinolysis giving special emphasis on their relation to inflammation control.
Targeted Analysis of Whole Genome Sequence Data to Diagnose Genetic Cardiomyopathy
Authors: Golbus Jessica R. , Puckelwartz Megan J. , Dellefave-Castillo Lisa , Fahrenbach John P. , Nelakuditi Viswateja , Pesce Lorenzo L. , Pytel Peter , McNally Elizabeth M. 
Published: September 2014

Background—
Cardiomyopathy is highly heritable but genetically diverse. At present, genetic testing for cardiomyopathy uses targeted sequencing to simultaneously assess the coding regions of >50 genes. New genes are routinely added to panels to improve the diagnostic yield. With the anticipated $1000 genome, it is expected that genetic testing will shift toward comprehensive genome sequencing accompanied by targeted gene analysis. Therefore, we assessed the reliability of whole genome sequencing and targeted analysis to identify cardiomyopathy variants in 11 subjects with cardiomyopathy.

Methods and Results—
Whole genome sequencing with an average of 37× coverage was combined with targeted analysis focused on 204 genes linked to cardiomyopathy. Genetic variants were scored using multiple prediction algorithms combined with frequency data from public databases. This pipeline yielded 1 to 14 potentially pathogenic variants per individual. Variants were further analyzed using clinical criteria and segregation analysis, where available. Three of 3 previously identified primary mutations were detected by this analysis. In 6 subjects for whom the primary mutation was previously unknown, we identified mutations that segregated with disease, had clinical correlates, and had additional pathological correlation to provide evidence for causality. For 2 subjects with previously known primary mutations, we identified additional variants that may act as modifiers of disease severity. In total, we identified the likely pathological mutation in 9 of 11 (82%) subjects.

Conclusions—
These pilot data demonstrate that ≈30 to 40× coverage whole genome sequencing combined with targeted analysis is feasible and sensitive to identify rare variants in cardiomyopathy-associated genes.
Assessment of Tracheostomy and Laryngectomy Knowledge among Nonotolaryngology Physicians
Authors: Robinson Aaron D. , Squires Lane D. , Kuhn Maggie , Brodie Hilary 
Published: September 2014

Objectives:(1) Assess the current fund of knowledge about alternate airways (tracheostomy and laryngectomy) among practicing physicians, residents, and senior medical students at University of California, Davis. (2) Identify knowledge deficits regarding alternate airways. (3) Assess the need for improved medical education about care of alternate airways.Methods:A cross‐sectional survey study at an academic medical center. An anonymous 10‐question, multiple‐choice survey was administered to senior medical students as well as resident and attending physicians at the University of California, Davis in the departments of Emergency Medicine, Family Medicine, General Surgery, Internal Medicine, Otolaryngology, Pediatrics, and Physical Medicine & Rehabilitation. Scores from the physicians in the Department of Otolaryngology–Head and Neck Surgery were compared with nonotolaryngology physician and medical student scores. These data were analyzed using analysis of variance.Results:Otolaryngology physicians scored an average of 98%, while nonotolaryngology physicians scored 58% and medical students scored 64% (P <. 05). Physicians’ self‐assessed comfort level with alternate airways was underestimated, when compared with their quiz score. Medical students who had participated in an otolaryngology rotation performed better than those who did not have a rotation (75% vs 40%).Conclusions:Individuals with alternate airways (tracheotomies or laryngectomies) are common, and their care demands a fundamental understanding of and comfort with their unique provision. Our preliminary findings identify significant knowledge gaps among nonotolaryngologists concerning the critical topic of alternate airways. These deficits underscore the importance of improving familiarity with alternate airways among nonotolaryngologists who are likely to encounter such individuals.
Early trends in invasive pneumococcal disease in children following the introduction of 13-valent pneumococcal conjugate vaccine: results from eight years of active surveillance in a Mexican hospital
Authors: Chacon-Cruz Enrigue , Rivas-Landeros R.M. , Volker-Soberanes M.L. 
Published: September 2014

Background: In May 2012, universal vaccination with the 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced for all children in the Tijuana region of Mexico, with a coverage of 80%. Method: Between October 2005 and September 2013 active surveillance was undertaken for all invasive pneumococcal diseases (IPDs) in children admitted to the Tijuana General Hospital. Results: Following PCV-13 implementation, there was a 75% reduction in overall IPD, and no cases of serotype 19A, pneumococcal meningitis, and pneumococcal-associated deaths. Conclusions: These results are the first to show the effectiveness of PCV-13 in Mexico.
Respiratory virus is a real pathogen in immunocompetent community-acquired pneumonia: comparing to influenza like illness and volunteer controls
Authors: Zhan Yangqing , Yang Zifeng , Chen Rongchang , Wang Yutao , Guan Wenda , Zhao Suishan 
Published: September 2014

AbstractBackgroundViral pathogens were more commonly reported than previously estimated in community-acquired pneumonia (CAP) patients. However, the real role of virus was still controversial.MethodsConsecutive adult patients with CAP between April and December, 2009 were prospectively enrolled. A four-fold or greater increase of IgG-titres against respiratory viruses in pair sera was tested by means of hemagglutination inhibition assay or indirect immunofluorescence. Swab samples were tested by cell culture and/or nucleic amplification tests. Viral etiology was considered definitive if at least one of the above tests was positive.ResultsViral etiology was established in fifty-two (34.9%) of 149 CAP patients, twenty-two (81.5%) of 27 influenza like illness patients, and none of 75 volunteer controls. Forty-seven CAP patients were infected by a single virus (24 influenza A virus, 5 influenza B, 10 parainfluenza virus type 3 [PIV-3], 2 PIV-1, 2 adenovirus, 2 human rhinovirus and 2 coronavirus OC43), five cases by two or three viruses co-infection. Fever ≥ 39°C (66.7%), fatigue (64.6%), and purulent sputum (52.1%) was the most common symptoms in viral pneumonia patients. On multivariate analysis, myalgia was included in the model for pneumonia associated with influenza infection. In the CURB-65 model only influenza infection was found independently associated with severe disease (CURB-65 score ≥ 3) out of variables, including age(years), sex, current smoking status, sick contact with febrile patients, numbers of comorbidity, presence of influenza infection, presence of PIV infection, with P = 0.021, OR 7.86 (95% CI 1.37-45.04).ConclusionRespiratory virus was not a bystander, but pathogenic in pneumonia and was a common cause of CAP.
Optimization of an organic photovoltaic device via modulation of thickness of photoactive and optical spacer layers
Authors: Li Qi , Yoon Won Jung , Ju Heongkyu 
Published: September 2014

Abstract
We examine the modulation effects of thicknesses of both a photoactive layer (a bulk-heterojunction (BHJ) of poly(3-hexylthiophene) and [6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM)) and an optical spacer of a transparent metal oxide, for power conversion efficiency optimization of organic photovoltaic devices. The redistribution of the optical intensity at the photoactive layer via the thickness modulation of both layers is taken into account, to produce three-dimensional (3D) plots as a function of both layer thicknesses of 0 to 400 nm range (5 nm step), for the device efficiency optimization. The modulation pattern of absorption is produced in the 3D plot as scanning the thicknesses of both layers as a result of modulation of interference between incoming and reflected light, which can be secured by changing the effective optical path length between two electrodes of a photovoltaic device. It is also seen that the case of inserting the spacer of the higher refractive index demands finer adjustment of the spacer layer thickness to achieve the optimum device efficiency.
In addition, the series resistance of the photoactive layer of the thickness range of 0 to 70 nm is taken into account to provide the 3D plots as a function of the scanned thicknesses of both layers. Inclusion of the series resistance of the photoactive layer, which is also the function of its thickness, in the simulation, indicates that the series resistance can influence qualitatively the dependence of power conversion efficiency (PCE) on the thicknesses of both layers. We also find that minimization of series resistance, e.g., by device annealing, allows not only the relevant voltage to increase but also the optimum thickness of the photoactive layer to increase, leading to more absorption of light.
Theoretical Study on the Relationship between the Geometric Change and the s–p Hybridization Formation of LiAln− Clusters (n = 3–13)
Authors: Ishibashi Chiaki , Matsuzawa Hidenori 
Published: September 2014

Abstract
The relationships between the geometric and electronic structures, and photoelectron spectra (PES) of LiAln− (n = 3–13) clusters were investigated. The ground and low-lying states geometries were optimized using B3LYP calculation. The assignment for large PES peaks was performed on the basis of calculated adiabatic detachment energies (ADE) and vertical detachment energies (VDE) values. PES peaks in Figure 2 of the clusters smaller than n = 6 are arose mostly from 3p of Al and those larger than n = 9 are 3s–3p (s–p) of Al. This peak pattern change occurs due to the s–p hybridization with the change in the geometric features. It was suggested that the high coordinated Al atom(s) in the Al framework and Li atom play an important role in forming the s–p hybridization at n ≥ 9.
Total hip replacement through a posterior approach using a 22 mm diameter femoral head
Authors: Kumar V. , Sharma S. , James J. , Hodgkinson J. P. , Hemmady M. V. 
Published: September 2014

Despite a lack of long-term follow-up, there is an increasing trend towards using femoral heads of large diameter in total hip replacement (THR), partly because of the perceived advantage of lower rates of dislocation. However, increasing the size of the femoral head is not the only way to reduce the rate of dislocation; optimal alignment of the components and repair of the posterior capsule could achieve a similar effect. In this prospective study of 512 cemented unilateral THRs (Male:Female 230:282) performed between 2004 and 2011, we aimed to determine the rate of dislocation in patients who received a 22 mm head on a 9/10 Morse taper through a posterior approach with capsular repair and using the transverse acetabular ligament (TAL) as a guide for the alignment of the acetabular component. The mean age of the patients at operation was 67 years (35 to 89). The mean follow-up was 2.8 years (0.5 to 6.6). Pre- and post-operative assessment included Oxford hip, Short Form-12 and modified University of California Los Angeles and Merle D’Aubigne scores. The angles of inclination and anteversion of the acetabular components were measured using radiological software. There were four dislocations (0.78%), all of which were anterior. In conclusion, THR with a 22 mm diameter head performed through a posterior approach with capsular repair and using the TAL as a guide for the alignment of the acetabular component was associated with a low rate of dislocation. Cite this article: Bone Joint J 2014;96-B:1202–6.
The use of a long stem cemented femoral component in revision total hip replacement
Authors: te Stroet M. A. J. , Bronsema E. , Rijnen W. H. C. , Gardeniers J. W. M. , Schreurs B. W. 
Published: September 2014

In this retrospective study, we investigated the results of revision total hip replacement (THR) using a cemented long-stemmed Exeter femoral component, with a minimum length of 205 mm in patients with extensive femoral bone defects. The study included 37 consecutive patients with a mean age of 76 years (39 to 93) and a mean follow-up of nine years (5 to 16). A total of 26 patients (70%) had a pre-operative Endo-Klinik score of 3 or 4. Impaction bone grafting was used in 24 patients (65%). At the time of evaluation, 22 patients (59%) were still alive and were evaluated clinically and radiologically. A total of 14 patients died during follow-up and their data were included until the time of their death. One reconstruction failed after five years and five months owing to recurrent dislocation: the hip was converted to an excision arthroplasty. Intra-operative fractures or fissures were encountered in nine patients (24%), but none occurred during impaction of the bone graft. Post-operative peri-prosthetic fractures occurred in two patients (5%); both were treated with plate fixation. At nine years, survival with the endpoint of all-cause re-revision was 96.3% (95% CI 76.4 to 99.5); including re-operations for any reason, it was 80.7% (95% CI 56.3 to 92.3%). There were no re-revisions for aseptic loosening.The survival of long stem cemented femoral components following revision THR is satisfactory in a fragile population with extensive femoral defects.Cite this article: Bone Joint J 2014; 96-B:1207–13.
An examination of the effect of different methods of scoring pain after a total knee replacement on the number of patients who report unchanged or worse pain
Authors: W-Dahl A. , Sundberg M. , Lidgren L. , Ranstam J. , Robertsson O. 
Published: September 2014

We identified a group of patients from the Swedish Arthroplasty Register who reported no relief of pain or worse pain one year after a total knee replacement (TKR). A total of two different patient-reported pain scores were used during this process. We then evaluated how the instruments used to measure pain affected the number of patients who reported no relief of pain or worse pain, and the relative effect of potential risk factors. Between 2008 and 2010, 2883 TKRs were performed for osteoarthritis in two Swedish arthroplasty units. After applying exclusion criteria, 2123 primary TKRs (2123 patients) were included in the study. The Knee injury and Osteoarthritis Outcome Score (KOOS) and a Visual Analogue Scale (VAS) for knee pain were used to assess patients pre-operatively and one year post-operatively. Only 50 of the 220 patients (23%) who reported no pain relief on either the KOOS pain subscale or the VAS for knee pain did so with both of these instruments. Patients who reported no pain relief on either measure tended to have less pain pre-operatively but a higher degree of anxiety. Charnley category C was a predictor for not gaining pain relief as measured on a VAS for knee pain. The number of patients who are not relieved of pain after a TKR differs considerably depending on the instrument used to measure pain. Cite this article: Bone Joint J 2014;96-B:1222–6.
Dysplasia of the contralateral hip in patients with unilateral late-detected congenital dislocation of the hip
Authors: Terjesen T. 
Published: September 2014

The aim of this study was to investigate the incidence of dysplasia in the ‘normal’ contralateral hip in patients with unilateral developmental dislocation of the hip (DDH) and to evaluate the long-term prognosis of such hips. A total of 48 patients (40 girls and eight boys) were treated for late-detected unilateral DDH between 1958 and 1962. After preliminary skin traction, closed reduction was achieved at a mean age of 17.8 months (4 to 65) in all except one patient who needed open reduction. In 25 patients early derotation femoral osteotomy of the contralateral hip had been undertaken within three years of reduction, and later surgery in ten patients. Radiographs taken during childhood and adulthood were reviewed. The mean age of the patients was 50.9 years (43 to 55) at the time of the latest radiological review. In all, eight patients (17%) developed dysplasia of the contralateral hip, defined as a centre-edge (CE) angle < 20° during childhood or at skeletal maturity. Six of these patients underwent surgery to improve cover of the femoral head; the dysplasia improved in two after varus femoral osteotomy and in two after an acetabular shelf operation. During long-term follow-up the dysplasia deteriorated to subluxation in two patients (CE angles 4° and 5°, respectively) who both developed osteoarthritis (OA), and one of these underwent total hip replacement at the age of 49 years. In conclusion, the long-term prognosis for the contralateral hip was relatively good, as OA occurred in only two hips (4%) at a mean follow-up of 50 years. Regular review of the ‘normal’ side is indicated, and corrective surgery should be undertaken in those who develop subluxation. Cite this article: Bone Joint J 2014; 96-B:1161–6.
Dilemmas in imaging for peri-acetabular osteotomy
Authors: Kosuge D. , Cordier T. , Solomon L. B. , Howie D. W. 
Published: September 2014

Peri-acetabular osteotomy is an established surgical treatment for symptomatic acetabular dysplasia in young adults. An anteroposterior radiograph of the pelvis is commonly used to assess the extent of dysplasia as well as to assess post-operative correction. Radiological prognostic factors include the lateral centre-edge angle, acetabular index, extrusion index and the acetabular version. Standing causes a change in the pelvis tilt which can alter certain radiological measurements relative to the supine position. This article discusses the radiological indices used to assess dysplasia and reviews the effects of patient positioning on these indices with a focus on assessment for a peri-acetabular osteotomy. Intra-operatively, fluoroscopy is commonly used and the implications of using fluoroscopy as a modality to assess the various radiological indices along with the effects of using an anteroposterior or posteroanterior fluoroscopic view are examined. Each of these techniques gives rise to a slightly different image of the pelvis as the final image is sensitive to the position of the pelvis and the projection of the x-ray beam. Cite this article: Bone Joint J 2014;96-B:1155–60.
Carpal tunnel decompression in the super-elderly
Authors: Stone O. D. , Clement N. D. , Duckworth A. D. , Jenkins P. J. , Annan J. D. , McEachan J. E. 
Published: September 2014

There is conflicting evidence about the functional outcome and rate of satisfaction of super-elderly patients (≥ 80 years of age) after carpal tunnel decompression. We compiled outcome data for 756 patients who underwent a carpal tunnel decompression over an eight-year study period, 97 of whom were super-elderly, and 659 patients who formed a younger control group (< 80 years old). There was no significant difference between the super-elderly patients and the younger control group in terms of functional outcome according to the mean (0 to 100) QuickDASH score (adjusted mean difference at one year 1.8; 95% confidence interval (CI) -3.4 to 7.0) and satisfaction rate (odds ratio (OR) 0.78; 95% CI 0.34 to 1.58). Super-elderly patients were, however, more likely to have thenar muscle atrophy at presentation (OR 9.2, 95% CI 5.8 to 14.6). When nerve conduction studies were obtained, super-elderly patients were more likely to have a severe conduction deficit (OR 12.4, 95% CI 3.0 to 51.3). Super-elderly patients report functional outcome and satisfaction rates equal to those of their younger counterparts. They are more likely to have thenar muscle atrophy and a severe nerve conduction deficit at presentation, and may therefore warrant earlier decompression. Cite this article: Bone Joint J 2014; 96-B:1234–8.