bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deescalating Adjuvant Trastuzumab in HER2-Positive Early-Stage Breast Cancer: A Systemic Review and Meta-Analysis
Authors: Goldvaser Hadar , Korzets Yasmin , Shepshelovich Daniel , Yerushalmi Rinat , Sarfaty Michal , Ribnikar Domen , Thavendiranathan Paaladinesh , Amir Eitan 
Published: April 2019

AbstractBackgroundOne year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results.MethodsA search of PubMed and abstracts from key conferences identified randomized trials that compared abbreviated trastuzumab therapy to 1 year of treatment in early-stage HER2-positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted for disease-free survival (DFS) and overall survival (OS). Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor expression, and the duration of abbreviated trastuzumab (9–12 weeks vs 6 months). Odds ratios (ORs) and 95% confidence intervals were computed for prespecified cardiotoxicity events including cardiac dysfunction and congestive heart failure. P values were two-sided.ResultsAnalysis included six trials comprising 11 603 patients. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI = 1.05 to 1.25, P  = .002) and OS (HR = 1.15, 95% CI = 1.02 to 1.29. P = .02). The effect on DFS was not influenced by estrogen receptor status (P for the subgroup difference = .23), nodal involvement (P = .44), or the different duration of trastuzumab in the experimental arm (P = .09). Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI = 0.55 to 0.81, P < .001) and congestive heart failure (OR = 0.66, 95% CI = 0.50 to 0.86, P = .003).ConclusionsCompared with 1 year, shorter duration of adjuvant trastuzumab is associated with statistically significantly worse DFS and OS despite favorable cardiotoxicity profile. One year of targeted HER2 treatment should remain the standard adjuvant treatment in early-stage HER2-positive disease with appropriate cardiac monitoring.
Genome-Wide Analysis of Glioblastoma Patients with Unexpectedly Long Survival
Authors: Richardson Timothy E , Patel Seema , Serrano Jonathan , Sathe Adwait Amod , Daoud Elena V , Oliver Dwight , Maher Elizabeth A , Madrigales Alejandra , Mickey Bruce E , Taxter Timothy , Jour George , White Charles L , Raisanen Jack M , Xing Chao , Snuderl Matija , Hatanpaa Kimmo J 
Published: April 2019

Abstract
Glioblastoma (GBM), representing WHO grade IV astrocytoma, is a relatively common primary brain tumor in adults with an exceptionally dismal prognosis. With an incidence rate of over 10 000 cases in the United States annually, the median survival rate ranges from 10–15 months in IDH1/2-wildtype tumors and 24–31 months in IDH1/2-mutant tumors, with further variation depending on factors such as age, MGMT methylation status, and treatment regimen. We present a cohort of 4 patients, aged 37–60 at initial diagnosis, with IDH1-mutant GBMs that were associated with unusually long survival intervals after the initial diagnosis, currently ranging from 90 to 154 months (all still alive). We applied genome-wide profiling with a methylation array (Illumina EPIC Array 850k) and a next-generation sequencing panel to screen for genetic and epigenetic alterations in these tumors. All 4 tumors demonstrated methylation patterns and genomic alterations consistent with GBM. Three out of four cases showed focal amplification of the CCND2 gene or gain of the region on 12p that included CCND2, suggesting that this may be a favorable prognostic factor in GBM. As this study has a limited sample size, further evaluation of patients with similar favorable outcome is warranted to validate these findings.
The new Hungarian asset management foundation
Authors: Menyhei Ákos 
Published: April 2019

Abstract
The most important global issues of wealth planning are privacy, asset protection, and tax compliance. The ultimate question is how these needs match with the current and future legal environment. Obviously, privacy is under attack and the implementation of the fifth Anti-Money Laundering Directive is sweeping away the remaining ruins of it. The separation of private and business assets is one of the bases of the legal work and, during the last 10 years, tax compliance was forced out by The Organisation for Economic Co-operation and Development (OECD) Member States, achieving the result that assets are declared and taxed. There is very little room for manoeuvre, if someone wants to achieve all three aims at once. The new Hungarian asset management foundation—a hybrid of a trust and a private foundation—provides an excellent solution to link privacy, asset protection, and tax compliance together.
“You Want Me to Assess What?”: Faculty Perceptions of Assessing Residents From Outside Their Specialty
Authors: Burm Sarah , Sebok-Syer Stefanie S. , Lingard Lorelei , VanHooren Tamara , Chahine Saad , Goldszmidt Mark , Watling Christopher J. 
Published: April 2019

Problem
Competency-based medical education (CBME) demands that residents be directly observed performing clinical tasks; however, many faculty lack assessment expertise, and some programs lack resources and faculty numbers to fulfill CBME’s mandate. To maximize limited faculty resources, the authors explored training and deploying faculty to assess residents in specialties outside their own.

Approach
In spring 2017, 10 MD and 2 PhD assessors at a medium-sized medical school in Ontario, Canada, participated in a 4-hour training session, which focused on providing formative assessments of patient handover, a core competency of medical practice. Assessors were deployed to 2 clinical settings outside their own specialty—critical care and pediatrics—each completing 11 to 26 assessments of residents delivering patient handover. Assessors were subsequently interviewed regarding their experiences.

Outcomes
While assessors felt able to judge handover performance outside their specialty, their sense of comfort varied with their own prior experiences in the given settings. Lack of familiarity with the process of handover in a specific setting directly influenced assessors’ perceptions of their own credibility. Although assessors identified the potential benefits of cross-specialty assessment, they also cited challenges to sustaining this approach.

Next Steps
Findings indicate a possible “contextual threshold” for cross-specialty assessment: tasks with high context specificity might not be suitable for cross-specialty assessment. Introducing higher-fidelity simulation into the training protocol and ensuring faculty members are remunerated for their time are necessary to establish future opportunities for shared assessment resources across training programs.
Intranasal Opioid-Induced Destruction of the Nose and Throat
Authors: Sutherland Laura , Sutherland Anne , Khalil Diana , Safneck Janice , Meen Eric 
Published: April 2019

Les opioïdes jouent un rôle important dans le traitement de la douleur de nombreux patients, mais sont de plus en plus associés au trouble de l’utilisation de substances et à des effets indésirables en Amérique du Nord. Dans cette étude de cas, nous décrivons le premier cas canadien de séquelles significatives intranasales et pharyngiques suite à l’utilisation d’opioïdes intranasaux. Les approches de diagnostic et de traitement sont ensuite décrites. Chez les patients présentant des représentations atypiques, les lésions tissulaires induites par les opioïdes intranasaux devraient être envisagées dans le diagnostic différentiel des lésions tumorales otolaryngologiques. Ce cas souligne l’importance de pouvoir reconnaître les complications otolaryngologiques de la mauvaise utilisation des opioïdes intranasaux et traiter ainsi de manière appropriée en utilisant une approche multidisciplinaire.

ABSTRACT
Opioids play an important part in the pain management of many patients, but are increasingly associated with substance use disorder and adverse events in North America. In this case report, we describe the first noted Canadian case of significant intranasal and pharyngeal sequelae of intranasal opioid use. Diagnostic and treatment approaches are then described. In patients with atypical presentations, intranasal opioid-induced tissue damage should be considered in the differential diagnosis of otolaryngologic tissue damage. This case highlights the importance of being able to recognize the otolaryngologic complications of intranasal opioid misuse and thereby appropriately treat using a multidisciplinary approach.
Leaving Hospital Against Medical Advice After Methadone Discontinuation in the Intensive Care Unit: A Case Report
Authors: Young Samantha , Ahamad Keith , Fairbairn Nadia 
Published: April 2019

ABSTRACT

Methadone is an effective and widely used opioid agonist treatment for reduction and cessation of illicit opioid use. Once a stable dose is achieved, interruptions in treatment are not recommended given the increased risk of relapse and the potential for overdose. Despite comprehensive clinical care guidance on the initiation and administration of methadone in the outpatient setting, there is limited guidance for the continuation of methadone in the hospital or critical care setting. Additionally, little is known about potential morbidity associated with methadone treatment interruption in hospital. This case describes the clinical course of a 58-year-old female who had been on a stable dose of methadone at 120 mg daily. She was admitted to the intensive care unit following the onset of decreased level of consciousness and hypoxia with subsequent respiratory failure. Although intubated in the intensive care unit, her methadone was discontinued. Given the length of time methadone was withheld, she required re-initiation at a dose of 30 mg daily. This led to severe withdrawal symptoms, use of illicit opioids while in hospital, and eventually leaving hospital prematurely against medical advice despite potentially life-threatening active medical issues. This case highlights the potential morbidity of methadone treatment interruption in the hospital setting. Additional research is needed to understand how to manage methadone and potential treatment interruptions during acute medical illness.
Dipyridamole Augments Three-Dimensionally Printed Bioactive Ceramic Scaffolds to Regenerate Craniofacial Bone
Authors: Lopez Christopher D. , Diaz-Siso J. Rodrigo , Witek Lukasz , Bekisz Jonathan M. , Gil Luiz F. , Cronstein Bruce N. , Flores Roberto L. , Torroni Andrea , Rodriguez Eduardo D. , Coelho Paulo G. 
Published: April 2019

Background:
Autologous bone grafts remain a standard of care for the reconstruction of large bony defects, but limitations persist. The authors explored the bone regenerative capacity of customized, three-dimensionally printed bioactive ceramic scaffolds with dipyridamole, an adenosine A2A receptor indirect agonist known to enhance bone formation.

Methods:
Critical-size bony defects (10-mm height, 10-mm length, full-thickness) were created at the mandibular rami of rabbits (n = 15). Defects were replaced by a custom-to-defect, three-dimensionally printed bioactive ceramic scaffold composed of β-tricalcium phosphate. Scaffolds were uncoated (control), collagen-coated, or immersed in 100 μM dipyridamole. At 8 weeks, animals were euthanized and the rami retrieved. Bone growth was assessed exclusively within scaffold pores, and evaluated by micro–computed tomography/advanced reconstruction software. Micro–computed tomographic quantification was calculated. Nondecalcified histology was performed. A general linear mixed model was performed to compare group means and 95 percent confidence intervals.

Results:
Qualitative analysis did not show an inflammatory response. The control and collagen groups (12.3 ± 8.3 percent and 6.9 ± 8.3 percent bone occupancy of free space, respectively) had less bone growth, whereas the most bone growth was in the dipyridamole group (26.9 ± 10.7 percent); the difference was statistically significant (dipyridamole versus control, p < 0.03; dipyridamole versus collagen, p < 0.01 ). There was significantly more residual scaffold material for the collagen group relative to the dipyridamole group (p < 0.015), whereas the control group presented intermediate values (nonsignificant relative to both collagen and dipyridamole). Highly cellular and vascularized intramembranous-like bone healing was observed in all groups.

Conclusion:
Dipyridamole significantly increased the three-dimensionally printed bioactive ceramic scaffold’s ability to regenerate bone in a thin bone defect environment.
Current Concepts in Feminizing Gender Surgery
Authors: Safa Bauback , Lin Walter C. , Salim Ali M. , Deschamps-Braly Jordan C. , Poh Melissa M. 
Published: April 2019

Learning Objectives:
After reading this article and viewing the video, the participant should be able to: 1. Discuss appropriate treatment guidelines, including preoperative mental health and hormonal treatment before gender-affirmation surgery. 2. Name various surgical options for facial, chest, and genital feminization. 3. Recognize key steps and anatomy during facial feminization, feminizing mammaplasty, and vaginoplasty. 4. Discuss major risks and complications of vaginoplasty.

Summary:
Transgender and gender-nonconforming individuals may experience conflict between their gender identity and their gender assigned at birth. With recent advances in health care and societal support, appropriate treatment has become newly accessible and has generated increased demand for gender-affirming care, which is globally guided by the World Professional Association for Transgender Health. This CME article reviews key terminology and standards of care, and provides an overview of various feminizing gender-affirming surgical procedures.
Accelerator-based X-ray sources: synchrotron radiation, X-ray free electron lasers and beyond
Authors: Ishikawa Tetsuya 
Published: April 2019

The evolution of synchrotron radiation (SR) sources and related sciences is discussed to explain the ‘generation’ of the SR sources. Most of the contemporary SR sources belong to the third generation, where the storage rings are optimized for the use of undulator radiation. The undulator development allowed to reduction of the electron energy of the storage ring necessary for delivering 10 keV X-rays from the initial 6–8 GeV to the current 3 Gev. Now is the transitional period from the double-bend-achromat lattice-based storage ring to the multi-bend-achromat lattice to achieve much smaller electron beam emittance. Free electron lasers are the other important accelerator-based light sources which recently reached hard X-ray regime by using self-amplified spontaneous emission scheme. Future accelerator-based X-ray sources should be continuous wave X-ray free electron lasers and pulsed X-ray free electron lasers. Some pathways to reach the future case are discussed.
This article is part of the theme issue ‘Fifty years of synchrotron science: achievements and opportunities’.
XMaS @ the ESRF
Authors: Bikondoa Oier , Bouchenoire Laurence , Brown Simon D. , Thompson Paul B. J. , Wermeille Didier , Lucas Chris A. , Cooper Malcolm J. , Hase Thomas P. A. 
Published: April 2019

This paper describes the motivation for the design and construction of a beamline at the European Synchrotron Radiation Facility (ESRF) for the use of UK material scientists. Although originally focused on the study of magnetic materials, the beamline has been running for 20 years and currently supports a very broad range of science as evidenced by the research topics highlighted in this article. We describe how the beamline will adapt to align with the ESRF's upgrade to a diffraction limited storage ring.This article is part of the theme issue ‘Fifty years of synchrotron science: achievements and opportunities’.
The development and exploitation of synchrotron single-crystal diffraction for chemistry and materials
Authors: Clegg William 
Published: April 2019

A historical account is given of the 25-year development of dedicated synchrotron beamlines for single-crystal diffraction as applied to the so-called small-molecule fields of chemistry and materials science. Designs have drawn on previous successful models in macromolecular crystallography, with appropriate modifications in view of the different properties and behaviour of the respective sample types. Key factors in making these facilities attractive and productive for users include familiarity of operational procedures and the availability of experimental techniques and features normally found in local chemical crystallography laboratories, especially for the handling of samples and processing of diffraction data. Beamlines dedicated to single-crystal diffraction rather than shared with other techniques can be optimized for effective and efficient use. The experience gained from the original design, development and exploitation of stations 9.8 and 16.2SMX at the Daresbury Laboratory Synchrotron Radiation Source and beamline 11.3.1 at the Advanced Light Source have led to highly productive current facilities at ALS beamline 12.2.1 and Diamond Light Source beamline I19, including the recent introduction of remote-access operation. Such facilities have generated and continue to provide major impact in academic and commercial research that could otherwise not be achieved, including patents and applications in pharmaceuticals, energy and gas storage systems, and government policy.
This article is part of the theme issue ‘Fifty years of synchrotron science: achievements and opportunities’.
Synchrotron radiation biomedical imaging and radiotherapy: from the UK to the Antipodes
Authors: Hall Christopher , Lewis Robert 
Published: April 2019

Although the general public might think of ‘X-rays’ as they are applied to imaging (radiography) and for the treatment of disease (radiotherapy), the use of synchrotron radiation (SR) X-ray beams in these areas of science was a minor activity 50 years ago. The largest gains in science from SR were seen to be in those areas where signals were weakest in laboratory instruments, such as X-ray diffraction and spectroscopy. As the qualities of SR X-rays were explored and more areas of science adopted SR-based methods, this situation changed. About 30 years ago, the clinical advantages of using SR X-ray beams for radiography, radiotherapy and clinical diagnostics started to be investigated. In the UK, a multi-disciplinary group, consisting of clinicians, medical physicists and other scientists working mainly with the Synchrotron Radiation Source (SRS) in Cheshire, started to investigate techniques for diagnosis and potentially a cure for certain cancers. This preliminary work influenced the design of new facilities being constructed around the world, in particular the Imaging and Medical Beam Line on the Australian Synchrotron in Melbourne. Two authors moved from the UK to Australia to participate in this exciting venture. The following is a personal view of some of the highlights of the early-year SRS work, following through to the current activities on the new facility in Australia.
This article is part of the theme issue ‘Fifty years of synchrotron science: achievements and opportunities’.
Transforming X-ray detection with hybrid photon counting detectors
Authors: Förster Andreas , Brandstetter Stefan , Schulze-Briese Clemens 
Published: April 2019

Hybrid photon counting (HPC) detectors have radically transformed basic research at synchrotron light sources since 2006. They excel at X-ray diffraction applications in the energy range from 2 to 100 keV. The main reasons for their superiority are the direct detection of individual photons and the accurate determination of scattering and diffraction intensities over an extremely high dynamic range. The detectors were first adopted in macromolecular crystallography where they revolutionized data collection. They were soon also used for small-angle scattering, coherent scattering, powder X-ray diffraction, spectroscopy and increasingly high-energy applications. Here, we will briefly survey the history of HPC detectors, explain their technology and then show in detail how improved detection has transformed a wide range of experimental techniques. We will end with an outlook to the future, which will probably see HPC technology find even broader use, for example, in electron microscopy and medical applications.
This article is part of the theme issue ‘Fifty years of synchrotron science: achievements and opportunities’.
Myosin XI Interacting with a RabE GTPase Is Required for Polarized Growth
Authors: Orr Robert G. , Furt Fabienne , Warner Erin L. , Agar Erin M. , Garbarino Jennifer M. , Cabral Sarah E. , Dubuke Michelle L. , Butt Allison M. , Munson Mary , Vidali Luis 
Published: April 2019

AbstractThe fundamental eukaryotic process of intracellular trafficking requires the interconnected activity of molecular motors trafficking vesicular cargo within a dynamic cytoskeletal network. However, in plants, few mechanistic details are known about how molecular motors associate with their secretory cargo to support the ubiquitous processes of polarized growth and cell division. A yeast two-hybrid screen of aPhyscomitrella patenslibrary identified a RabE GTPase as an interactor of myosin XI and subsequently demonstrated all five RabE members interact with myosin XI. Consistent with a role in polarized transport, we observed RabE at the growing cell apex and at the expanding cell plate during cell division. An in vivo cross-correlation analysis of fluorescently tagged RabE and myosin XI revealed that both species are spatiotemporally coupled, demonstrating their simultaneous involvement in polarized growth. To determine if myosin XI and RabE are directly coupled, we first computationally predicted myosin XI:RabE interface through a homology modeling-directed approach. We identified a structurally conserved residue on myosin XI, V1422, that when mutated abolished RabE binding in the yeast two-hybrid system and resulted in unpolarized plants instead of the characteristic network of filamentous cells when regenerated from single cells. Together, this work demonstrates the requirement of a direct myosin XI:RabE interaction for polarized growth in plants.
Long read sequencing reveals a novel class of structural aberrations in cancers: identification and characterization of cancerous local amplifications
Authors: Sakamoto Yoshitaka , Xu Liu , Seki Masahide , Yokoyama Toshiyuki T. , Kasahara Masahiro , Kashima Yukie , Ohashi Akihiro , Shimada Yoko , Motoi Noriko , Tsuchihara Katsuya , Kobayashi Susumu , Kohno Takashi , Shiraishi Yuichi , Suzuki Ayako , Suzuki Yutaka 
Published: April 2019

AbstractHere we report identification of a new class of local structural aberrations in lung cancers. The whole-genome sequencing of cell lines using a long read sequencer, PromethION, demonstrated that typical cancerous mutations, such as point mutations, large deletions and gene fusions can be detected also on this platform. Unexpectedly, we revealed unique structural aberrations consisting of complex combinations of local duplications, inversions and micro deletions. We further analyzed and found that these mutations also occurin vivo, even in key cancer-related genes. These mutations may elucidate the molecular etiology of patients for whom causative cancerous events and therapeutic strategies remain elusive.