bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Tumor Mitochondrial DNA Content Is Associated with Better Outcome in Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy
Authors: Weerts Marjolein J.A. , Hollestelle Antoinette , Sieuwerts Anieta M. , Foekens John A. , Sleijfer Stefan , Martens John W.M. 
Published: April 2017

Abstract
Purpose: In this study, we aimed to explore whether low levels of mitochondrial DNA (mtDNA) content in the primary tumor could predict better outcome for breast cancer patients receiving anthracycline-based therapies. We hypothesized that tumor cells with low mtDNA content are more susceptible to mitochondrial damage induced by anthracyclines, and thus are more susceptible to anthracycline treatment.
Experimental Design: We measured mtDNA content by a qPCR approach in 295 primary breast tumor specimens originating from two well-defined cohorts: 174 lymph node–positive patients who received adjuvant chemotherapy and 121 patients with advanced disease who received chemotherapy as first-line palliative treatment. The chemotherapy regimens given were either anthracycline-based (FAC/FEC) or methotrexate-based (CMF).
Results: In both the adjuvant and advanced settings, we observed increased benefit for patients with low mtDNA content in their primary tumor, but only when treated with FAC/FEC. In multivariable Cox regression analysis for respectively distant metastasis-free survival and progression-free survival, the HR for the FAC/FEC-treated mtDNA low group in the adjuvant setting was 0.46 [95% confidence interval (CI), 0.24–0.89; P = 0.020] and in the advanced setting 0.49 (95% CI, 0.27–0.90; P = 0.022) compared with the FAC/FEC-treated mtDNA high group. We did not observe these associations in the patients treated with CMF.
Conclusions: In our two study cohorts, breast cancer patients with low mtDNA content in their primary tumor had better outcome from anthracycline-containing chemotherapy. The frequently observed decrease in mtDNA content in primary breast tumors may be exploited by guiding chemotherapeutic regimen decision making. Clin Cancer Res; 23(16); 4735–43. ©2017 AACR.
Geologia e geofísica do greenstone belt Vila Nova, porção NE do Cráton Amazônico, Amapá, Brasil
Authors: Borghetti Cristiano , Philipp Ruy Paulo 
Published: April 2017

Poucos afloramentos e um acentuado intemperismo caracterizam a região do greenstone belt Vila Nova, no sudeste do Amapá. Este artigo vale-se de dados aerogeofísicos na interpretação geológica e estrutural durante o mapeamento geológico, objetivando aumentar o entendimento geológico e tectônico dessa porção do Cráton Amazônico. A interpretação qualitativa das imagens magnetométricas e gama-espectrométricas geradas para o projeto foi efetuada em ambiente de Sistema de Informações Geográficas (SIG). O reconhecimento de unidades magnetométricas e gamaespectrométricas presentes na área de estudo teve como base a classificação hierárquica dos polígonos delineados pela interpretação visual. A partir dessa análise foram delimitados os principais domínios geológicos e definidos os traçados geológico-estruturais, em conjunto com dados geológicos de campo, dados geofísicos e da análise petrográfica. Essa integração permitiu delimitar as rochas das áreas do embasamento arqueano composto por ortognaisses e granitóides do Complexo Tumucumaque, as rochas metavulcano‑sedimentares do Complexo Vila Nova e os maciços graníticos intrusivos de idade paleoproterozoica. A integração entre os dados geofísicos e de campo resultou no aumento da definição da cartografia geológica, ressaltando-se a importância dessa metodologia para o reconhecimento de tramas estruturais e litológicas complexas em áreas de pouca exposição e dificuldade de acesso.
Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy
Authors: Fourey Dana , Care Melanie , Siminovitch Katherine A. , Weissler-Snir Adaya , Hindieh Waseem , Chan Raymond H. , Gollob Michael H. , Rakowski Harry , Adler Arnon 
Published: April 2017

Background—
Available data suggests that double mutations in patients with hypertrophic cardiomyopathy are not rare and are associated with a more severe phenotype. Most of this data, however, is based on noncontemporary variant classification.

Methods and Results—

Clinical data of all hypertrophic cardiomyopathy patients with 2 rare genetic variants were retrospectively reviewed and compared with a group of patients with a single disease-causing variant. Furthermore, a literature search was performed for all studies with information on prevalence and outcome of patients with double mutations. Classification of genetic variants was reanalyzed according to current guidelines. In our cohort (n=1411), 9% of gene-positive patients had 2 rare variants in sarcomeric genes but only in 1 case (0.4%) were both variants classified as pathogenic. Patients with 2 rare variants had a trend toward younger age at presentation when compared with patients with a single mutation. All other clinical variables were similar. In data pooled from cohort studies in the literature, 8% of gene-positive patients were published to have double mutations. However, after reanalysis of reported variants, this prevalence diminished to 0.4%. All patients with 2 radical mutations in
MYBPC3
in the literature had severe disease with death or heart transplant during the first year of life. Data on other specific genotype–phenotype correlations were scarce.

Conclusions—

Double mutations in patients with hypertrophic cardiomyopathy are much less common than previously estimated. With the exception of double radical
MYBPC3
mutations, there is little data to guide clinical decision making in cases with double mutations.
Incremental Value of Transthoracic Doppler Echocardiography‐Assessed Coronary Flow Reserve in Patients With Suspected Myocardial Ischemia Undergoing Myocardial Perfusion Scintigraphy
Authors: Gan Li‐Ming , Svedlund Sara , Wittfeldt Ann , Eklund Charlotte , Gao Sinsia , Matejka Göran , Jeppsson Anders , Albertsson Per , Omerovic Elmir , Lerman Amir 
Published: April 2017

Background

Adenosine‐assisted transthoracic Doppler‐derived coronary flow reserve (
TDE
‐
CFR
) reflects coronary vascular function. The prognostic and incremental value of left anterior descending coronary artery
TDE
‐
CFR
above myocardial perfusion scintigraphy in patients with suspected myocardial ischemia has not yet been studied.

Methods and Results

Three hundred seventy‐one patients (mean age, 62.3±8.7 years; 46.8% males) referred to myocardial perfusion scintigraphy attributed to suspected myocardial ischemia were included in the study. The
TDE
‐
CFR
result was blinded to the referring physician. Patients were followed up regarding major cardiovascular events, defined as cardiovascular death, myocardial infarction, or acute revascularization during a median follow‐up time of 4.5 years. A
TDE
‐
CFR
value of ≤2.0 was considered reduced. Major cardiovascular events occurred during follow‐up in 60 patients (16.2%). A reduced
TDE
‐
CFR
was detected in 76 patients (20.5%). Patients with reduced
TDE
‐
CFR
had an event rate of 36.8% compared to 10.8% in patients with normal
TDE
‐
CFR
(unadjusted hazard ratio, 4.63; 95% CI, 2.78–7.69;
P
<0.001). In a multivariate model,
TDE
‐
CFR
remained a significant independent predictor of major cardiovascular events. The major cardiovascular events rate was 7.5% in patients without myocardial perfusion scintigraphy‐detected myocardial ischemia and normal
TDE
‐
CFR
(n=200), 24.2% in patients without ischemia but with reduced
TDE
‐
CFR
(n=33), and 46.5% in patients with both myocardial perfusion scintigraphy–detected myocardial ischemia and a reduced
TDE
‐
CFR
(n=43;
P
<0.001).

Conclusions

Coronary microvascular dysfunction, as determined by
TDE
‐
CFR,
is a strong independent predictor of cardiovascular events and adds incremental prognostic value compared with myocardial perfusion scintigraphy. The current study supports routine assessment of
CFR
in patients with suspected ischemic heart disease.
L’auteur des Rasāʾil Ikhwān al-Ṣafāʾ selon les sources ismaéliennes ṭayyibites
Authors: De Smet Daniel 
Published: April 2017

L’identité des auteurs desRasāʾil Ikhwān al-Ṣafāʾet leur affiliation à l’ismaélisme demeurent un sujet controversé dans la recherche moderne. Les ismaéliens de tradition ṭayyibite attribuent lesÉpîtres, y compris laRisāla al-Jāmiʿa, à « la personne éminente » (al-shakhṣ al-fāḍil), qui ne serait autre que « Aḥmad », un des mystérieux imams cachés entre le 7eimam Muḥammad b. Ismāʿīl et le premier calife fatimide ʿAbd Allāh al-Mahdī. Aḥmad aurait entrepris la composition desÉpîtres, censées contenir la « vraie » philosophie telle qu’elle fut enseignée par les imams, pour contrecarrer le projet du calife abbasside al-Maʾmūn. Celui-ci est accusé de vouloir ruiner l’islam en faisant traduire en arabe des ouvrages écrits par des auteurs païens hostiles aux prophètes et aux imams. LesRasāʾil Ikhwān al-Ṣafāʾferaient ainsi contrepoids au mouvement de traduction gréco-arabe patronné par les Abbassides à Bagdad. Dans ma contribution, j’essaie de retracer la genèse de cette théorie en examinant les sources ismaéliennes, ṭayyibites en particulier.The identity of the authors of theRasāʾil Ikhwān al-Ṣafāʾand their relation with the Ismaʿili movement still are highly controversial issues. The Ṭayyibī Ismaʿilis ascribe theRasāʾil, along with theRisāla al-Jāmiʿa, to « the eminent person » (al-shakhṣ al-fāḍil), often identified with « Aḥmad », one of the mysterious hidden imams between the seventh imam Muḥammad b. Ismāʿīl and the first Fatimid caliph ʿAbd Allāh al-Mahdī. This Aḥmad is supposed to have composed theEpistles, containing the « true » philosophy as it was taught by the imams, in order to neutralize the impious project of the Abbasid caliph al-Maʾmūn, suspected to have commissioned Arabic translations of pagan Greek books, with the sole aim of undermining Islam. TheRasāʾil Ikhwān al-Ṣafāʾare thus presented as a counterpart to the Greco-Arabic translation movement patronized by the Abbasids in Bagdad. In the present paper I examine the formation of this theory, based on Ismaʿili sources belonging mainly to the Ṭayyibī tradition.
Testosterone suppression with a unique form of leuprorelin acetate as a solid biodegradable implant in patients with advanced prostate cancer: results from four trials and comparison with the traditional leuprorelin acetate microspheres formulation
Authors: Solarić Mladen , Bjartell Anders , Thyroff-Friesinger Ursula , Meani Davide 
Published: April 2017

Background: There are two slow-release ready-to-use forms of leuprorelin acetate (1-month and 3-month) that are available as solid, biodegradable implants for the treatment of advanced, hormone-sensitive prostate cancer. These implants have been shown to be as effective as traditional leuprorelin acetate microspheres for achieving successful testosterone suppression (⩽0.5 ng/ml) and lowering prostate-specific antigen (PSA) levels. Here we further evaluate testosterone suppression levels from four clinical trials evaluating the 3-month leuprorelin implant, including analysis below the European Association of Urology (EAU) castration level (<0.2 ng/ml). Methods: Studies were conducted in patients with locally advanced/metastatic prostate cancer: (1) a randomised, controlled single-dose study comparing the leuprorelin implant with leuprorelin microspheres; (2) a single-arm, single-dose study of the leuprorelin implant; (3 and 4) two long-term studies with the leuprorelin implant administered twice, 12 or 16 weeks apart. Patients received 3-month leuprorelin (5 mg) implant or 3-month leuprorelin (10.72 mg) microspheres. Testosterone levels were analysed using radioimmunoassay or ultrasensitive liquid chromatography tandem mass spectrometry. Results: Both the leuprorelin implant and the leuprorelin microspheres achieved mean testosterone suppression (⩽0.5 ng/ml) within 4 weeks for >3 months. In both long-term, single-arm studies with the leuprorelin implant, median values of testosterone ⩽0.2 ng/ml were achieved at Week 4 and maintained until study completion (6 and 8 months); PSA decrease was also observed versus baseline. Conclusions: Long-lasting steady serum levels of testosterone, comparable with orchiectomy and consistent with the EAU-recommended castration level (<0.2 ng/ml), were achieved at Week 4 and maintained up to 8 months in men with advanced prostate cancer who received the leuprorelin implant.
Phosphodiesterase type 5 inhibitor to riociguat transition is associated with hemodynamic and symptomatic improvement in pulmonary hypertension
Authors: Davey Ryan , Benza Raymond L. , Murali Srinivas , Raina Amresh 
Published: April 2017

Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. We studied the clinical and hemodynamics effects of transitioning 12 pulmonary hypertension patients from Phosphodiesterase type 5 inhibitor (PDE5i) to riociguat, and demonstrated a significant increase in cardiac index, fall in pulmonary vascular resistance, and improvement in functional class with this switch. Switch from PDE5i to riociguat appeared to be safe and fairly well tolerated in most patients.
Achieving optimal technology use: A proposed model for health technology reassessment
Authors: Soril Lesley JJ , MacKean Gail , Noseworthy Tom W , Leggett Laura E , Clement Fiona M 
Published: April 2017

Background: Healthcare providers, managers and policy-makers in many jurisdictions are focused on a common goal: optimizing value and quality of care provided to their citizens within a resource envelope. Health technology reassessment is a structured, evidence-based assessment of the clinical, social, ethical and economic effects of a technology currently used in the healthcare system to inform optimal use of that technology in comparison with its alternatives. There are, however, few practical experiences with health technology reassessment and, as such, a nascent theoretical and methodological base. Health technology reassessment is a key strategy to achieve optimal healthcare resource utilization, and establishing a model for health technology reassessment is a required methodological step. Methods and results: The purpose of this article is to answer three formative questions: (1) What is health technology reassessment? (2) When should a health technology reassessment be implemented? (3) What is the role of health technology reassessment in evidence-informed health policy? Finally, we propose a conceptual framework for health technology reassessment, which others can modify, adapt, or adopt in their own context. The model consists of three broad phases and six iterative stages: (1) identification, (2) prioritization, (3) evidence synthesis, (4) determine policy/practice recommendation, (5) policy/practice implementation and (6) monitoring and evaluation. Two foundational components (meaningful stakeholder engagement and ongoing knowledge exchange and utilization) are represented across all stages. Conclusion: This description of health technology reassessment and the proposed model can be used by healthcare policy-makers and researchers to advance the field of technology management, with the goal of achieving optimal use throughout a technology’s lifecycle.
Iatrogenic Spinal Cord Injury Resulting From Cervical Spine Surgery
Authors: Daniels Alan H. , Hart Robert A. , Hilibrand Alan S. , Fish David E. , Wang Jeffrey C. , Lord Elizabeth L. , Buser Zorica , Tortolani P. Justin , Stroh D. Alex , Nassr Ahmad , Currier Bradford L. , Sebastian Arjun S. , Arnold Paul M. , Fehlings Michael G. , Mroz Thomas E. , Riew K. Daniel 
Published: April 2017

Study Design: Retrospective cohort study of prospectively collected data. Objective: To examine the incidence of iatrogenic spinal cord injury following elective cervical spine surgery. Methods: A retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network was conducted. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, were reviewed to identify occurrence of iatrogenic spinal cord injury. Results: In total, 3 cases of iatrogenic spinal cord injury following cervical spine surgery were identified. Institutional incidence rates ranged from 0.0% to 0.24%. Of the 3 patients with quadriplegia, one underwent anterior-only surgery with 2-level cervical corpectomy, one underwent anterior surgery with corpectomy in addition to posterior surgery, and one underwent posterior decompression and fusion surgery alone. One patient had complete neurologic recovery, one partially recovered, and one did not recover motor function. Conclusion: Iatrogenic spinal cord injury following cervical spine surgery is a rare and devastating adverse event. No standard protocol exists that can guarantee prevention of this complication, and there is a lack of consensus regarding evaluation and treatment when it does occur. Emergent imaging with magnetic resonance imaging or computed tomography myelography to evaluate for compressive etiology or malpositioned instrumentation and avoidance of hypotension should be performed in cases of intraoperative and postoperative spinal cord injury.
C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases
Authors: Thompson Sara E. , Smith Zachary A. , Hsu Wellington K. , Nassr Ahmad , Mroz Thomas E. , Fish David E. , Wang Jeffrey C. , Fehlings Michael G. , Tannoury Chadi A. , Tannoury Tony , Tortolani P. Justin , Traynelis Vincent C. , Gokaslan Ziya , Hilibrand Alan S. , Isaacs Robert E. , Mummaneni Praveen V. , Chou Dean , Qureshi Sheeraz A. , Cho Samuel K. , Baird Evan O. , Sasso Rick C. , Arnold Paul M. , Buser Zorica , Bydon Mohamad , Clarke Michelle J. , De Giacomo Anthony F. , Derakhshan Adeeb , Jobse Bruce , Lord Elizabeth L. , Lubelski Daniel , Massicotte Eric M. , Steinmetz Michael P. , Smith Gabriel A. , Pace Jonathan , Corriveau Mark , Lee Sungho , Cha Peter I. , Chatterjee Dhananjay , Gee Erica L. , Mayer Erik N. , McBride Owen J. , Roe Allison K. , Yanez Marisa Y. , Stroh D. Alex , Than Khoi D. , Riew K. Daniel 
Published: April 2017

Study Design: A multicenter, retrospective review of C5 palsy after cervical spine surgery. Objective: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. Methods: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ2 tests or Fisher exact tests for categorical variables. Results: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). Conclusion: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date.
Intraoperative Death During Cervical Spinal Surgery: A Retrospective Multicenter Study
Authors: Wang Jeffrey C. , Buser Zorica , Fish David E. , Lord Elizabeth L. , Roe Allison K. , Chatterjee Dhananjay , Gee Erica L. , Mayer Erik N. , Yanez Marisa Y. , McBride Owen J. , Cha Peter I. , Arnold Paul M. , Fehlings Michael G. , Mroz Thomas E. , Riew K. Daniel 
Published: April 2017

Study Design: A retrospective multicenter study. Objective: Routine cervical spine surgeries are typically associated with low complication rates, but serious complications can occur. Intraoperative death is a very rare complication and there is no literature on its incidence. The purpose of this study was to determine the intraoperative mortality rates and associated risk factors in patients undergoing cervical spine surgery. Methods: Twenty-one surgical centers from the AOSpine North America Clinical Research Network participated in the study. Medical records of patients who received cervical spine surgery from January 1, 2005, to December 31, 2011, were reviewed to identify occurrence of intraoperative death. Results: A total of 258 patients across 21 centers met the inclusion criteria. Most of the surgeries were done using the anterior approach (53.9%), followed by posterior (39.1%) and circumferential (7%). Average patient age was 57.1 ± 13.2 years, and there were more male patients (54.7% male and 45.3% female). There was no case of intraoperative death. Conclusions: Death during cervical spine surgery is a very rare complication. In our multicenter study, there was a 0% mortality rate. Using an adequate surgical approach for patient diagnosis and comorbidities may be the reason how the occurrence of this catastrophic adverse event was prevented in our patient population.
Mean grain diameters from thin sections: matching the average to the problem
Authors: Farr Robert S. , Honour Victoria C. , Holness Marian B. 
Published: April 2017

AbstractIt is common practice to estimate a mean diameter for spherical or sub-spherical particles or vesicles in a rock by multiplying the average diameter of the approximately circular cross-sections visible in thin section by a factor of 1.273. This number-weighted average may be dominatedby the hard-to-measure fine tail of the size distribution, and is unlikely to be representative of the average particle diameter of greatest interest for a wide range of geological problems or processes. Average particle size can be quantified in a variety of ways, based on the mass or surfacearea of the particles, and here we provide exact relations of these different average measures to straightforward measurements possible in thin section, including an analysis of how many particles to measure to achieve a desired level of uncertainty. The use of average particle diameter isillustrated firstly with a consideration of the accumulation of olivine phenocrysts on the floor of the 135 m thick picrodolerite/crinanite unit of the Shiant Isles Main Sill. We show that the 45 m thick crystal pile on the sill floor could have formed by crystal settling within about a year.The second geological example is provided by an analysis of the sizes of exsolved Fe-rich droplets during unmixing of a basaltic melt in a suite of experimental charges. We show that the size distribution cannot be explained by sudden nucleation, followed by either Ostwald ripening or Browniancoalescence. We deduce that a continuous process of droplet nucleation during cooling is likely to have occurred.