bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of heart-specific small subunit of myosin light chain phosphatase results in heart failure and conduction disturbance
Authors: Arimura Takuro , Muchir Antoine , Kuwahara Masayoshi , Morimoto Sachio , Ishikawa Taisuke , Du Cheng-Kun , Zhan Dong-Yun , Nakao Shu , Machida Noboru , Tanaka Ryo , Yamane Yoshihisa , Hayashi Takeharu , Kimura Akinori 
Published: February 2018

Mutations in genes encoding components of the sarcomere cause cardiomyopathy, which is often associated with abnormal Ca2+sensitivity of muscle contraction. We have previously shown that a heart-specific myosin light chain phosphatase small subunit (hHS-M21) increases the Ca2+sensitivity of muscle contraction. The aim of the present study was to investigate the function of hHS-M21in vivo and the causative role of abnormal Ca2+sensitivity in cardiomyopathy. We generated transgenic mice with cardiac-specific overexpression of hHS-M21. We confirmed that hHS-M21increased the Ca2+sensitivity of cardiac muscle contraction in vivo, which was not followed by an increased phosphorylation of myosin light chain 2 isoforms. hHS-M21transgenic mice developed severe systolic dysfunction with myocardial fibrosis and degeneration of cardiomyocytes in association with sinus bradycardia and atrioventricular conduction defect. The contractile dysfunction and cardiac fibrosis were improved by treatment with the Rho kinase inhibitor fasudil. Our findings suggested that the overexpression of hHS-M21results in cardiac dysfunction and conduction disturbance via non-myosin light chain 2 phosphorylation-dependent regulation.NEW & NOTEWORTHY The present study is the first to develop mice with transgenic overexpression of a heart-specific myosin light chain phosphatase small subunit (hHS-M21) and to examine the effects of hHS-M21on cardiac function. Elevation of hHS-M21induced heart failure with myocardial fibrosis and degeneration of cardiomyocytes accompanied by supraventricular arrhythmias.
Targeted Therapies for Targeted Populations: Anti-EGFR Treatment for EGFR-Amplified Gastroesophageal Adenocarcinoma
Authors: Maron Steven B. , Alpert Lindsay , Kwak Heewon A. , Lomnicki Samantha , Chase Leah , Xu David , O'Day Emily , Nagy Rebecca J. , Lanman Richard B. , Cecchi Fabiola , Hembrough Todd , Schrock Alexa , Hart John , Xiao Shu-Yuan , Setia Namrata , Catenacci Daniel V.T. 
Published: February 2018

Abstract
Previous anti-EGFR trials in unselected patients with gastroesophageal adenocarcinoma (GEA) were resoundingly negative. We identified EGFR amplification in 5% (19/363) of patients at the University of Chicago, including 6% (8/140) who were prospectively screened with intention-to-treat using anti-EGFR therapy. Seven patients received ≥1 dose of treatment: three first-line FOLFOX plus ABT-806, one second-line FOLFIRI plus cetuximab, and three third/fourth-line cetuximab alone. Treatment achieved objective response in 58% (4/7) and disease control in 100% (7/7) with a median progression-free survival of 10 months. Pretreatment and posttreatment tumor next-generation sequencing (NGS), serial plasma circulating tumor DNA (ctDNA) NGS, and tumor IHC/FISH for EGFR revealed preexisting and/or acquired genomic events, including EGFR-negative clones, PTEN deletion, KRAS amplification/mutation, NRAS, MYC, and HER2 amplification, and GNAS mutations serving as mechanisms of resistance. Two evaluable patients demonstrated interval increase of CD3+ infiltrate, including one who demonstrated increased NKp46+, and PD-L1 IHC expression from baseline, suggesting an immune therapeutic mechanism of action. EGFR amplification predicted benefit from anti-EGFR therapy, albeit until various resistance mechanisms emerged.
Significance: This paper highlights the role of EGFR inhibitors in EGFR-amplified GEA—despite negative results in prior unselected phase III trials. Using serial ctDNA and tissue NGS, we identified mechanisms of primary and acquired resistance in all patients, as well as potential contribution of antibody-dependent cell-mediated cytotoxicity to their clinical benefit. Cancer Discov; 8(6); 696–713. ©2018 AACR.
See related commentary by Strickler, p. 679.
This article is highlighted in the In This Issue feature, p. 663
Hemodynamic Characteristics in Significant Symptomatic and Asymptomatic Primary Mitral Valve Regurgitation at Rest and During Exercise
Authors: Bakkestrøm Rine , Banke Ann , Christensen Nicolaj L. , Pecini Redi , Irmukhamedov Akhmadjon , Andersen Mads , Borlaug Barry A. , Møller Jacob E. 
Published: February 2018

Background—
In severe asymptomatic primary mitral valve regurgitation without risk factors, surgery strategy is controversial. We sought to clarify whether being symptomatic corresponds to the hemodynamic burden and reduced exercise capacity. A better understanding of this may contribute to optimize timing of surgery.

Methods and Results—

Subjects with asymptomatic (New York Heart Association functional class I, n=29) or symptomatic (New York Heart Association functional class II and III, n=28) significant primary mitral valve regurgitation (effective regurgitant orifice, ≥0.30 cm
2
; left ventricular ejection fraction, >60%) were included. Right heart catheterization during rest and exercise, echocardiography, magnetic resonance imaging, and peak oxygen consumption test was performed. Symptomatic subjects had significantly higher pulmonary capillary wedge pressure at rest (14±4 versus 11±3 mm Hg;
P
=0.003) and at maximal exercise (30±6 versus 25±7 mm Hg;
P
=0.02) and higher mean pulmonary artery pressure (PAP) at rest (22±7 versus 18±4 mm Hg;
P
=0.005) and maximal exercise (46±8 versus 39±7 mm Hg;
P
=0.005) than asymptomatic subjects. Among asymptomatic subjects with normal resting value, exercise testing revealed a systolic PAP >60 mm Hg in 34%. Also the reverse response with minimal increase in pulmonary capillary wedge pressure and mean PAP during exercise was seen, especially in asymptomatic subjects. Among symptomatic subjects, we found a significant inverse correlation between resting mean PAP and left ventricular ejection fraction (
r
=−0.52;
P
=0.02) and right ventricular ejection fraction (
r
=−0.67;
P
<0.01). Peak oxygen consumption was equal and normal in both groups and correlated with left ventricular stroke volume but not with pulmonary capillary wedge pressure.

Conclusions—
Symptoms in patients with severe mitral valve regurgitation relate to congestion (pulmonary capillary wedge pressure and PAP), but not to peak oxygen consumption, which is determined by forward left ventricular stroke volume. Exercise testing reveals a higher mitral valve regurgitation burden in apparently asymptomatic patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02961647.
Public Interest Environmental Litigation in China
Authors: Zhang Richard , Mayer Benoit 
Published: February 2018

Abstract
Since January 2015, China’s Environmental Protection Law has allowed Chinese Non- Government Organisations to initiate public interest litigation in relation to activities that harm the environment. This article assesses the implementation of this reform. Based on a variety of primary and secondary sources, it documents almost every case filed in the first two-and-a-half years of the implementation of public interest environmental litigation in China. It demonstrates a rapid development of this new field of litigation which, so far, has almost systematically led to Court decisions favourable to the plaintiffs. Yet, we also recognize some limitations and room for improvement, in particular regarding barriers to access to courts and questions of enforcement of judgments. Therefore, while public interest environmental litigation is a promising opportunity for the protection of the environment in China, some possible refinements of the relevant statutory framework can be identified.
Euro-Atlantic Atmospheric Circulation during the Late Maunder Minimum
Authors: Mellado-Cano Javier , Barriopedro David , García-Herrera Ricardo , Trigo Ricardo M. , Álvarez-Castro Mari Carmen 
Published: February 2018

Abstract
This paper presents observational evidence of the atmospheric circulation during the Late Maunder Minimum (LMM, 1685–1715) based on daily wind direction observations from ships in the English Channel. Four wind directional indices and 8-point wind roses are derived at monthly scales to characterize the LMM. The results indicate that the LMM was characterized by a pronounced meridional circulation and a marked reduction in the frequency of westerly days all year round, as compared to the present (1981–2010). The winter circulation contributed the most to the cold conditions. Nevertheless, findings indicate that the LMM in Europe was more heterogeneous than previously thought, displaying contrasting spatial patterns in both circulation and temperature, as well as large decadal variability. In particular, there was an increase of northerly winds favoring colder winters in the first half of the LMM, but enhanced southerlies contributing to milder conditions in the second half of the LMM. The analysis of the atmospheric circulation yields a new and complete classification of LMM winters. The temperature inferred from the atmospheric circulation confirms the majority of extremely cold winters well documented in the literature, while uncovering other less documented cold and mild winters. The results also suggest a nonstationarity of the North Atlantic Oscillation (NAO) pattern within the LMM, with extremely cold winters being driven by negative phases of a “high zonal” NAO pattern and “low zonal” NAO patterns dominating during moderately cold winters.
On Strangers and Commensurability in Eurasia: A View from ‘the North’
Authors: Sartori Paolo 
Published: February 2018

Sanjay Subrahmanyam, Three Ways to be Alien: Travails and Encounters in the Early Modern World, Delhi: Permanent Black, 2011, 228 pp. Sanjay Subrahmanyam, Courtly Encounters: Translating Courtliness and Violence in Early Modern Eurasia, Cambridge, MA: Harvard University Press, 2012, 312 pp.
A Study of the Relationship of Parent-Adolescent Communication, Self-Esteem, and God Image
Authors: Chartier Myron R. , Goehner Larry A. 
Published: February 2018

Eighty-four tenth and eleventh graders from a Christian high school in Southern California constituted the sample for this study. Three paper and pencil tests were administered to the subjects in order to measure the relationships of parental communication, self-esteem, and God image. The data from the tests were submitted to appropriate statistical procedures. Significant relationships were found to exist between parental communication and self-esteem, between self-esteem and God image, and between practical communication and the adolescents’ image of God. The results were discussed.
Breast tomosynthesis for the clarification of mammographic BI-RADS 3 lesions can decrease follow-up examinations and enables immediate cancer diagnosis
Authors: Bahrs Sonja D , Otto Vanessa , Hattermann Valerie , Klumpp Bernhard , Hahn Markus , Nikolaou Konstantin , Siegmann-Luz Katja 
Published: February 2018

Background The limited sensitivity of mammography in case of a high breast density often produces unclear or false-positive findings, so-called BI-RADS 3 lesions, which have to be followed up to prove benignity. Digital breast tomosynthesis (DBT) was developed to reduce such summation effects. Purpose To evaluate the influence of an additional DBT on the management of mammographic BI-RADS 3 findings and whether DBT can decrease the time to definitive diagnosis or not. Material and Methods We analyzed 87 patients with a mammographic non-calcified BI-RADS 3 lesion who underwent an additional DBT of the affected breast. A follow-up two-dimensional (2D) examination or a histological result of the lesion had to be available. The images were analyzed especially for the BI-RADS category and incremental diagnostic accuracy. Moreover, the inter-reader reliability and the radiation dose were evaluated. Results The BI-RADS category has been changed by the addition of DBT: 57.1% were assessed as BI-RADS 1 or 2, 4.6% as BI-RADS 4, and only 38.3% remained as BI-RADS 3. The intraclass correlation coefficient for the three readers showed a good agreement for inter-reader reliability. No false-negative examination was found in the follow-ups. Nine lesions were biopsied (seven benign, two malignant). Both malignant lesions were suspicious in the DBT (BI-RADS 4). A significant higher glandular dose was necessary for the DBT. Conclusion DBT has the potential to reduce the recall-rate of BI-RADS 3 lesions and to find and diagnose malignant lesions earlier than 2D mammography alone.
Mammographic screening attendance among immigrant and minority women: a systematic review and meta-analysis
Authors: Bhargava Sameer , Moen Kåre , Qureshi Samera Azeem , Hofvind Solveig 
Published: February 2018

Background Groups of immigrant and minority women are more often diagnosed with advanced stage breast cancer than other women. Mammographic screening aims to reduce mortality from breast cancer through early detection in asymptomatic women. Purpose To compare mammographic screening attendance among immigrant and minority women to that of other women. Material and Methods A literature search of PubMed, Embase, Google Scholar, and Cochrane identified 1369 papers published between January 1995 and March 2016. In the review, we included 33 studies investigating mammographic screening attendance among immigrant and/or minority women. In a meta-analysis, we included 19 of the studies that compared attendance among immigrant and/or minority women with that among other women, using a random effects model. Results The review included studies from Europe, North America, and Oceania, with 42,666,093 observations of opportunities for mammographic screening. Attendance was generally lower among immigrant and minority women compared to other women (46.2% vs. 55.0%; odds ratio = 0.64, 95% confidence interval = 0.56–0.73; P < 0.05, I2 = 99.9%). Non-Western immigrants had lower attendance rates than other immigrants. Conclusion Immigrant and minority women had lower mammographic screening attendance than other women, which could potentially put them at increased risk for more advanced breast cancer. This review emphasizes the importance of continued efforts to engage with the preventative health needs of diverse populations in attempts to achieve equality in access to, and use of, care.
Endovascular treatment for the control of active vaginal bleeding from uterine cervical cancer treated with radiotherapy
Authors: Chen Cheng Shi , Park Sohee , Shin Ji Hoon , Nouri Yasir , Kim Jong-Woo , Yoon Hyun-Ki , Ko Gi-Young 
Published: February 2018

Background Endovascular treatment has become a significant therapeutic option for the management of intractable bleeding in gynecologic malignancies. However, the endovascular treatment types were almost never mentioned when active bleeding from different arteries was identified. Purpose To present angiographic details and evaluate clinical efficacy of endovascular treatments to control active vaginal bleeding in uterine cervical cancer patients treated with radiotherapy. Material and Methods In this retrospective study, six, consecutive cervical cancer patients treated with radiotherapy who underwent endovascular treatment for active vaginal bleeding were included. Angiographic findings, endovascular treatment details, and clinical outcomes were obtained. Results Ten endovascular procedures were technically successful, in which bleeding arteries were the internal iliac artery/its branches (n = 5), external iliac artery (EIA) (n = 3), uterine artery (n = 1), and superior rectal artery (n = 1), and bleeding manifested as contrast extravasation (n = 6), pseudoaneurysm (n = 1), or both (n = 3). Three of the four repeated procedures showed different bleeding sites from the primary ones. Stent graft was inserted to preserve the patency of the bleeding EIA in two patients. For another EIA rupture, both proximal and distal embolization were performed, followed by femoral-to-femoral bypass to preserve blood flow. Bleeding control within one month was achieved in 80% (8/10). One minor complication, mild transient pelvic pain, occurred in one patient. Conclusions Various endovascular treatment was feasible and effective to control active vaginal bleeding from cervical cancer. Repeated procedures showed commonly different bleeding foci and stent graft insertion was effective for preserving the patency of the large bleeding artery.
Influence of Diagnosis and Other Factors on Patients’ Expectations of Foot and Ankle Surgery
Authors: Cody Elizabeth A. , Do Huong T. , Koltsov Jayme C. B. , Mancuso Carol A. , Ellis Scott J. 
Published: February 2018

Background: Many patient factors have been associated with higher or lower expectations of orthopedic surgery. In foot and ankle surgery, the diverse diagnoses seen may also influence expectations. The aim of this study was to investigate the relationship between diagnosis and patients’ preoperative expectations of elective foot and ankle surgery. Methods: Two hundred seventy-eight patients undergoing elective foot or ankle surgery for 1 of 7 common diagnoses were enrolled in a prospective cohort study. Preoperative expectations were assessed with the Hospital for Special Surgery Foot & Ankle Surgery Expectations Survey. Patients also completed the Foot & Ankle Outcome Score, Short Form 12, pain visual analog scale, and questionnaires for depressive and anxiety symptoms. Demographic and clinical data were collected. Patient factors and diagnosis were analyzed using multivariate regression analysis to identify independent predictors of higher expectations and determine the effect of diagnosis relative to other patient factors on expectations. Results: The multivariate regression analysis adjusting for demographics and other clinical characteristics showed that diagnosis contributed the most to the model, accounting for 10.5% of the variation in expectations survey scores. Patients with mid- or hindfoot arthritis ( P < .001), hallux valgus ( P = .001), or hallux rigidus ( P = .005) had lower scores (lower expectations) than those with ankle instability or osteochondral lesion. In the model, female sex ( P = .001), non-Caucasian race ( P = .031), and lower scores on the Foot & Ankle Outcome Score daily activities subscale ( P = .024) were associated with higher scores. Conclusions: Diagnosis of ankle instability or osteochondral lesion, female sex, non-Caucasian race, and lower Foot & Ankle Outcome Score daily activities subscale score were all associated with higher expectations. These findings may help inform and guide surgeons as they counsel patients preoperatively. Level of Evidence: Level II, cross-sectional study.
Outcomes After Primary Repair of Insertional Ruptures of the Achilles Tendon
Authors: Schipper Oliver N. , Anderson Robert B. , Cohen Bruce E. 
Published: February 2018

Background: Achilles tendon insertional sleeve avulsions occur when the Achilles distal tendon sleeve ruptures off of its insertion into the calcaneal tuberosity, sometimes with a small bony fragment from calcific tendinosis. Little evidence exists describing the outcomes and rerupture rate after operative management of Achilles tendon sleeve avulsions. Methods: A retrospective chart review was performed to identify patients who sustained an Achilles sleeve avulsion injury treated with operative repair between October 2005 and July 2014. A cohort of 16 patients from the general population and 12 professional athletes were included in the study. The primary outcome variable was rerupture of the Achilles tendon or need for revision surgery. Secondary outcome variables included the Coughlin Satisfaction Scale, visual VR-12, and Foot and Ankle Ability Measure (FAAM). Results: In the general population cohort, median follow-up was 8.1 years (range, 3.2-11.1 years). The median FAAM Activities of Daily Living score was 100 (range, 42.9-106), and the median FAAM Sports score was 100 (range, 7.1-103.6). The median VR-12 Mental Component Score was 66.9 (range, 45.6-71.8), and the median VR-12 Physical Component Score was 53 (range, 30.8-57.5). In the cohort of professional athletes, preceding insertional Achilles symptoms were present in 91.7% (11/12) of athletes for more than 9 months prior to rupture. All athletes returned to play with an average time of 13.4 months. No patients sustained a rerupture in the follow-up period. Conclusion: Operative repair of Achilles tendon sleeve avulsions was safe and effective with high patient satisfaction and good clinical outcomes in patients from the general population. Level of Evidence: Level IV, retrospective case series.
Integration of clinical pharmacists into an ambulatory, pediatric hematology/oncology/transplant clinic
Authors: Defoe Kimberly D , Jupp Jennifer , Leslie Tara 
Published: February 2018

Objectives To describe key activities performed by a newly deployed clinical pharmacist in an outpatient pediatric hematology, oncology, transplant clinic. To demonstrate how utilization of the pharmacist evolved, as indicated by changes in frequency of key activities, during the first four months of integration. Design Clinical pharmacists were made consistently available in an outpatient clinic serving hematology, oncology, transplant patients and their families. A list of key activities, based on provincial clinical pharmacist standards, was created to provide a framework for the role. Over a four-month period, the pharmacists recorded the number of times activities were performed. Results Over the data collection period, obtaining best possible medication histories (203), providing medication counseling (150), and creating adherence aids (144) were the most commonly performed activities. In comparison to the first month, key activities increased by 73% in the fourth month. Notably, providing recommendations for drug therapy (156%), assessments of adherence (122%), and best possible medication history collection (88%) increased considerably. Conclusions The integration of a pharmacist into an outpatient pediatric hematology, oncology, transplant clinic resulted in the provision of several key clinical pharmacy services. As the role developed, activities were performed more frequently, demonstrating growth in utilization of the pharmacist.