bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deleting Full Length Titin Versus the Titin M-Band Region Leads to Differential Mechanosignaling and Cardiac Phenotypes
Authors: Radke Michael H. , Polack Christopher , Methawasin Mei , Fink Claudia , Granzier Henk L. , Gotthardt Michael 
Published: January 2019

Background:
Titin is a giant elastic protein that spans the half-sarcomere from Z-disk to M-band. It acts as a molecular spring and mechanosensor and has been linked to striated muscle disease. The pathways that govern titin-dependent cardiac growth and contribute to disease are diverse and difficult to dissect.

Methods:
To study titin deficiency versus dysfunction, the authors generated and compared striated muscle specific knockouts (KOs) with progressive postnatal loss of the complete titin protein by removing exon 2 (E2-KO) or an M-band truncation that eliminates proper sarcomeric integration, but retains all other functional domains (M-band exon 1/2 [M1/2]-KO). The authors evaluated cardiac function, cardiomyocyte mechanics, and the molecular basis of the phenotype.

Results:
Skeletal muscle atrophy with reduced strength, severe sarcomere disassembly, and lethality from 2 weeks of age were shared between the models. Cardiac phenotypes differed considerably: loss of titin leads to dilated cardiomyopathy with combined systolic and diastolic dysfunction—the absence of M-band titin to cardiac atrophy and preserved function. The elastic properties of M1/2-KO cardiomyocytes are maintained, while passive stiffness is reduced in the E2-KO. In both KOs, we find an increased stress response and increased expression of proteins linked to titin-based mechanotransduction (CryAB, ANKRD1, muscle LIM protein, FHLs, p42, Camk2d, p62, and Nbr1). Among them, FHL2 and the M-band signaling proteins p62 and Nbr1 are exclusively upregulated in the E2-KO, suggesting a role in the differential pathology of titin truncation versus deficiency of the full-length protein. The differential stress response is consistent with truncated titin contributing to the mechanical properties in M1/2-KOs, while low titin levels in E2-KOs lead to reduced titin-based stiffness and increased strain on the remaining titin molecules.

Conclusions:
Progressive depletion of titin leads to sarcomere disassembly and atrophy in striated muscle. In the complete knockout, remaining titin molecules experience increased strain, resulting in mechanically induced trophic signaling and eventually dilated cardiomyopathy. The truncated titin in M1/2-KO helps maintain the passive properties and thus reduces mechanically induced signaling. Together, these findings contribute to the molecular understanding of why titin mutations differentially affect cardiac growth and have implications for genotype-phenotype relations that support a personalized medicine approach to the diverse titinopathies.
The tadpole of Hylodes babax Heyer, 1982 (Amphibia, Anura, Hylodidae)
Authors: PIRANI RENATA MAGALHÃES , PEZZUTI TIAGO LEITE , MOTTA ANA PAULA , FEIO RENATO NEVES 
Published: January 2019

Frog species from the genus Hylodes Fitzinger occur mainly in southeastern Brazil (Frost, 2010). Of the 24 species of genus only 13 species have their tadpoles described (see Discussion below). Hylodes babax was known from the type-locality at Caparaó mountain range (Heyer, 1982), and has recently been recorded from two new localities: Parque Estadual da Serra do Brigadeiro, in the Mantiqueira mountain range, and Floresta Estadual do Uaimií, in the southern Espinhaço mountain range (Pirani et al. 2010).
Frequency and radiological characteristics of previously overlooked renal cell carcinoma
Authors: Borkmann Simon , Geterud Kjell , Lundstam Sven , Hellström Mikael 
Published: January 2019

Background A majority of renal tumors are incidentally detected and may therefore have been previously radiologically overlooked. Purpose To investigate the frequency of previously radiologically overlooked renal cell carcinoma (RCC), identify tumor characteristics and imaging factors that contribute to misdiagnoses and to investigate its consequences. Material and Methods All RCCs identified in a regional cancer registry over one year were retrieved (n = 87). All preceding radiological examinations were re-analyzed for overlooked RCCs. Results RCCs had been previously overlooked in 18 (21%) of the 87 patients (on 26 examinations: computed tomography [CT] = 16, magnetic resonance imaging [MRI] = 5, urography = 3, ultrasound = 2) or 18 (43%) of the 42 patients who had earlier radiological examinations. Overlooked RCCs were smaller than non-overlooked RCCs (median = 23 mm; range = 10–45 mm vs. 65 mm; range = 13–207 mm) ( P < 0.0001), more frequently located in upper pole, 50% vs. 26% ( P = 0.0836), and more frequently homogenous, 50% vs. 9% ( P = 0.0003). There was no difference in exophytic growth (60% vs. 60%) ( P = 0.74). Overlooked RCCs displayed poorer visualization on CT/MRI in all image planes (axial, coronal, sagittal) compared to non-overlooked tumors ( P = 0.004, P = 0.001, P < 0.0001, respectively). Overlooked tumors had interval size progression of median 12 mm (range = 0–65 mm) to clinical detection (median = 1033 days). Conclusions RCCs are frequently overlooked at imaging in the clinical routine. Overlooked tumors were smaller and displayed poorer visualization in all image planes compared to non-overlooked tumors. Substantial delay to clinical diagnosis and variable size progression was noted. Careful attention to the kidneys in multiple image planes seems warranted, irrespective of clinical indication.
Incidence of rare cancers in the city of São Paulo, Brazil
Authors: Bustamante-Teixeira Maria Teresa , Latorre Maria do Rosário D.O. , Guerra Maximiliano R. , Tanaka Luana F. , Botta Laura , Trama Annalisa , Gatta Gemma 
Published: January 2019

Introduction: Rare cancers are a challenge for clinical practice as well as for epidemiology and public health. Studies on this subject are few and limited to the study of cases with scarce epidemiologic information. This study aimed to evaluate the incidence of rare cancers and to compare the demographic, anatomic, and histologic characteristics of rare and nonrare (common) cancers. Methods: Incidence data were obtained from the Population-based Cancer Registry of São Paulo, Brazil. Rare neoplasms were those defined in the RARECARE list, which takes into account an incidence lower than 6/100,000/year. Results: In São Paulo, 20.4% of tumors had an incidence lower than 6/100,000/year from 1997 to 2012, being therefore considered as rare tumors. We identified 11 entities with an incidence greater than 6/100,000/year (common neoplasms) and 186 entities with an incidence lower than 6/100,000/year (rare neoplasms). The mean annual incidence of all cancers was 365 per 100,000 in São Paulo between 1997 and 2012, and the incidence of all rare tumors was 74.5 per 100,000. Conclusions: This study presents the burden of rare cancers in Brazil. It is expected to be an incentive for further studies of these entities in order to know the epidemiologic profile of rare tumors in Brazil and to provide a more effective diagnostic and therapeutic approach.
Examining Barriers and Facilitators to Delivering SNAP-Ed Direct Nutrition Education in Rural Communities
Authors: Haynes-Maslow Lindsey , Osborne Isabel , Pitts Stephanie Jilcott 
Published: January 2019

Purpose: To better understand the barriers to implementing Supplemental Nutrition Assistance Program Education (SNAP-Ed) direct education programming in rural communities, as well as strategies to overcome these barriers. This includes (1) barriers to implementing direct education in rural communities, and (2) facilitators to overcoming direct-education barriers in rural communities. Design: This was a qualitative study that included in-depth interviews. Setting: Fifteen states across all 7 SNAP-Ed regions. Participants: Participants were eligible if they (1) were SNAP-Ed staff who were involved with implementing programs; (2) implemented at least 50% of their programming in rural communities, and (3) worked in their role for at least 12 months. Twenty-seven (n = 27) staff participated in interviews. Measures: Online surveys ascertained if participants were interested in participating in a 60-minute interview about implementing SNAP-Ed in rural communities. Interviews were semistructured and focused on the barriers and facilitators to implementing SNAP-Ed direct-education nutrition programming in rural areas. Analysis: Qualitative interviews were analyzed using content analysis in Atlas.ti. Results: Barriers to implementing direct education in rural communities included lack of healthy food and physical activity infrastructure to reinforce messages taught in class, funding restrictions, transportation for SNAP-Ed staff and the perception that this was also a problem for participants, and SNAP-Ed staff being seen as “outsiders” (not from the community). Facilitators included partnering with other organizations to increase recruitment and retention of SNAP-Ed participants, buy-in from local leaders, and SNAP-Ed staff being from the community. Conclusion: Partnerships between SNAP-Ed programs and non-SNAP-Ed organizations were essential in helping to recruit and retain participants. The SNAP-Ed staff should get buy-in from local leaders before starting direct-education programming. The SNAP-Ed programs should explore innovative delivery modalities including online and text messaging due to transportation issues in widespread rural geographies. Lastly, more work should be done to complement SNAP-Ed direct education with policy, systems, and environmental change initiatives.
The Stock Performance of American Companies Investing in a Culture of Health
Authors: Goetzel Ron Z. , Fabius Raymond , Roemer Enid Chung , Kent Karen B. , Berko Jeffrey , Head Michael A. , Henke Rachel Mosher 
Published: January 2019

Purpose: We investigated the relationship between companies’ efforts to build internal (COH-INT) and external cultures of health (COH-EXT) and their stock performance. Design: We administered 2 surveys, which measure companies’ programs, policies, and supports for improving the health of their employees and communities. We then compared the companies’ stock performance to the Standard and Poor’s (S&P) 500 Index from January 2013 through August 2017. Setting: United States. Participants: Representatives from 17 publicly traded companies who completed the COH-INT survey, of whom 14 also completed the COH-EXT. Measures: Culture of health scores were dichotomized into high versus low for both surveys. Stock price data for all companies were gathered from public sources. Analysis: We constructed 5 stock portfolios: all 17 companies, high COH-INT, low COH-INT, high COH-EXT, and low COH-EXT companies. We examined total returns for each portfolio compared to the S&P 500. Results: High COH-INT companies’ stock price appreciated by 115% compared to the S&P benchmark (+69%), while low COH-INT companies appreciated only 43%. In contrast, high COH-EXT companies underperformed (+44%) when compared to the S&P 500 (+69%) and low COH-EXT companies (+89%). Conclusion: This study supports the view that employers’ efforts to build an internal culture of health is a sound business strategy. More research is needed, however, to establish whether a link exists between supporting healthy community initiatives and company stock performance.
Not Only for the (Tom) boys: Gender Variables as Predictors for Playing Motivations, Passion, and Addiction for MMORPGs
Authors: Kneer Julia , Franken Sanne , Reich Sabine 
Published: January 2019

Background. Research on playing motivation and passion for MMORPGs and gender has so far mainly focused on biological sex and neglected variables related to social gender such as masculinity and femininity. As some playing motivations and obsessive passion are assumed to be related to problematic game play, problematic game play is still considered a male phenomenon, often based on mainly male samples and disregarding underlying causes in problematic tendencies that could explain or extent findings on biological sex difference. Method. This survey based quantitative study investigated the impact of masculine and feminine personality on game play motivations, passion, and problematic game play. Massively multiplayer online role-playing games (MMORPGs) players ( N = 375, 44.3% female) were recruited via Facebook and online games. Feminine and masculine personality traits were assessed along with game play motivations, passion, and problematic game play. Results. Stepwise regression analyses revealed that gender traits add significant value for almost all variables of interest. Negative masculine traits were positive predictors for achievement as game play motivation while positive feminine traits predicted social interaction. Harmonious passion was predicted by positive masculine traits. Negative feminine traits were found to predict immersion as well as obsessive passion and were also important for problematic game play. Conclusion. Gender traits add valuable information to mere biological sex concerning different game related concepts such as motivation, passion, and problematic game play. Despite the idea that problematic game play is a male phenomenon, negative feminine traits seem to be linked to problematic tendencies. We suggest including gender and personality variables for future games and/or media studies.
Regional differences in ischemic stroke in India (north vs. south)
Authors: Venugopalan Vishnu Y , Bhatia Rohit , Pandian Jeyaraj , Khurana Dheeraj , Kaul Subhash , Sylaja P.N. , Arora Deepti , Khatter Himani , Padma M.V. , Singhal Aneesh B. 
Published: January 2019

Background India is a large country with geographically diverse populations and varying risk factors. Identification of regional differences can improve healthcare policy decisions. Aim To study regional differences in stroke between North and South India. Methods We analyzed data from the Indo-US Collaborative Stroke Project, a National Institute of Health-funded multicentre prospective study conducted in five academic centers in India with a US-based coordinating center. Risk factors, severity, mechanisms, management, complications, and outcomes among ischemic stroke patients were compared between North and South Indian centers. Results Of the 2066 patients enrolled from North ( n = 1060) and South India ( n = 1006), North Indian patients were significantly older with fewer men and had lower rates of diabetes (32.8% vs. 38.7%, p < 0.01), dyslipidemia (3.5% vs. 25.7%, p < 0.01), tobacco use (27% vs. 38%, p < 0.001), and alcohol use (30.1% vs. 38.6%, p < 0.01). North Indian patients had higher median National Institute of Health stroke scale scores (10 vs. 9, p < 0.01), more frequent large-artery atherosclerosis mechanism (34% vs. 25.6%, p < 0.001), intravenous thrombolysis (14.0% vs. 6.1%, p < 0.001), and lower rates of pneumonia (10.5% vs. 15.1%, p = 0.02). The three-month outcome (modified Rankin Scale score 0–2, 45.8% vs. 50.3%, p = 0.08) did not differ; however, North Indian patients had higher 90-day mortality (23.5% vs. 13.5%, p < 0.0001). Conclusions The substantial regional differences in stroke risk factors and mechanisms may be partly explained by factors such as differing dietary habits and lifestyle, which can be addressed at a national level. Differences in acute and inpatient stroke care suggest a need for better adoption of national stroke management guidelines.
MHC class II cell-autonomously regulates self-renewal and differentiation of normal and malignant B cells
Authors: Merkenschlager Julia , Eksmond Urszula , Danelli Luca , Attig Jan , Young George R. , Nowosad Carla , Tolar Pavel , Kassiotis George 
Published: January 2019

AbstractBest known for presenting antigenic peptides to CD4+ T cells, major histocompatibility complex class II (MHC II) also transmits or may modify intracellular signals. Here, we show that MHC II cell-autonomously regulates the balance between self-renewal and differentiation in B-cell precursors, as well as in malignant B cells. Initiation of MHC II expression early during bone marrow B-cell development limited the occupancy of cycling compartments by promoting differentiation, thus regulating the numerical output of B cells. MHC II deficiency preserved stem cell characteristics in developing pro-B cells in vivo, and ectopic MHC II expression accelerated hematopoietic stem cell differentiation in vitro. Moreover, MHC II expression restrained growth of murine B-cell leukemia cell lines in vitro and in vivo, independently of CD4+ T-cell surveillance. Our results highlight an important cell-intrinsic contribution of MHC II expression to establishing the differentiated B-cell phenotype.
Randomized study of imatinib for chronic myeloid leukemia: comparing standard dose escalation with aggressive escalation
Authors: Miyamura Koichi , Ohnishi Kazunori , Ohtake Shigeki , Usui Noriko , Nakaseko Chiaki , Fujita Hiroyuki , Fujisawa Shin , Sakura Toru , Okumura Hirokazu , Iriyama Noriyoshi , Emi Nobuhiko , Fujimaki Katsumichi , Honda Sumihisa , Miyazaki Yasushi , Naoe Tomoki 
Published: January 2019

AbstractIn 2007, we conducted a prospective randomized study to compare an aggressive dose escalation (group B, n = 123) with the standard dose escalation proposed by European LeukemiaNet (group A, n = 122). In group B, if patients did not achieve a complete cytogenetic response (CCyR) at 3 months or did not achieve a major molecular response (MR3) at 6 months, imatinib was increased to 600 mg. At 6 months CCyR was achieved in 69.4% and 78.7% of patients in groups A and B, respectively. The rate of MR3 at 12 months and 24 months were similar in group A (52.1% and 70.0%) and group B (58.7% and 68.3%). The cumulative incidence of withdrawal by failure without accelerated/blast phase was higher in group A than in group B (9.2% vs 2.5% at 24 months). At 3 and 6 months, the protocol called for the imatinib dose to increase to 600 mg in 90 patients (74.4%) in group B. Among the 42 patients who received increased dose according to the protocol, 25 (60.0%) achieved MR3 at 12 months, whereas only 14 (35.0%) of 40 patients who did not receive an increased dose achieved MR3 (P &lt; .05). The number of patients who withdrew from this study was similar (group A, 20%; group B, 21%). The early aggressive dose escalation failed to produce a better molecular response at 12 months. However, for patients who tolerate imatinib well, but show inadequate response at an early time point, aggressive dose escalation may contribute to achieving a better outcome. This study was registered at http://www.umin.ac.jp/ctr/ as #R000000965.
Gene-based FVIIa prophylaxis modulates the spontaneous bleeding phenotype of hemophilia A rats
Authors: Zintner Shannon M. , Small Juliana C. , Pavani Giulia , Dankner Lynn , Marcos-Contreras Oscar A. , Gimotty Phyllis A. , Kjelgaard-Hansen Mads , Wiinberg Bo , Margaritis Paris 
Published: January 2019

Abstract
A sizable proportion of hemophilia inhibitor patients fails immune tolerance induction and requires bypass agents for long-term bleed management. Recombinant human-activated coagulation Factor VII (rhFVIIa) is an on-demand bypass hemostatic agent for bleeds in hemophilia inhibitor patients. Prophylactic use of rhFVIIa may enable sustained hemostatic management of inhibitor patients, but the critical relationship of rhFVIIa circulating levels and clinical outcome in that setting remains unclear. To address this in vivo, we used the rat hemophilia A (HA) model that exhibits spontaneous bleeds and allows longitudinal studies with sufficient statistical power. We simulated activated Factor VII (FVIIa) prophylaxis by adeno-associated virus (AAV) gene transfer of a rat FVIIa transgene. Compared with naive HA animals, rat FVIIa continuous expression affected the overall observed bleeds, which were resolved with on-demand administration of recombinant rat FVIIa. Specifically, although 91% of naive animals exhibited bleeds, this was reduced to 83% and 33% in animals expressing less than 708 ng/mL (&lt;14 nM) and at least 708 ng/mL (≥14 nM) rat FVIIa, respectively. No bleeds occurred in animals expressing higher than 1250 ng/mL (&gt;25 nM). Rat FVIIa expression of at least 708 ng/mL was also sufficient to normalize the blood loss after a tail vein injury. Continuous, AAV-mediated rat FVIIa transgene expression had no apparent adverse effects in the hemostatic system of HA rats. This work establishes for the first time a dose dependency and threshold of circulating FVIIa antigen levels for reduction or complete elimination of bleeds in a setting of FVIIa-based HA prophylaxis.
Non-base wage components as a source of wage adaptability to shocks: evidence from European firms, 2010–2013
Authors: Babecký Jan , Berson Clémence , Fadejeva Ludmila , Lamo Ana , Marotzke Petra , Martins Fernando , Strzelecki Pawel 
Published: January 2019

AbstractThis paper provides evidence on the role of non-base wage components as a channel for firms to adjust labour costs in the event of adverse shocks. It uses data from a firm-level survey for 25 European countries that covers the period 2010–2013. We find that firms subject to nominal wage rigidities, which prevent them from adjusting base wages, are more likely to cut non-base wage components when they are hit by negative shocks. Firms thus use non-base wage components as a strategic margin to overcome base wage rigidity. We also show that while non-base wage components exhibit some degree of downward rigidity this is smaller than that observed for base wages.
Evaluating the Impact of Treatment Care Planning on Quality Measures
Authors: Rocque Gabrielle B. , Williams Courtney P. , Hathaway Amanda R. , Halilova Karina I. , Stricker Carrie T. , Coombs Nicholas C. , Dudley William N. , Thomas Kathryn A. , Gaguski Michele , Crist Stéphanie , Kozlik Mary May , Larkin Patti , Cadden Austin , Jones Meredith I. 
Published: January 2019

PURPOSE: The Center for Medicare & Medicaid Innovation Oncology Care Model (OCM) requires documentation of a 13-point Institute of Medicine care management plan for Medicare patients. In addition, OCM includes evaluation of quality using key performance measures that align with the ASCO Quality Oncology Practice Initiative (QOPI). Both efforts are designed to improve patient-centered care and foster patients’ engagement in their care plan. METHODS: A multicenter quality improvement project was conducted to develop a strategy to meet the OCM treatment planning (TP) requirement (Plan), pilot clinician education coupled with use of electronic TP in early-stage breast cancer (Do), evaluate the impact of TP on QOPI measures (Study), and develop recommendations for future implementation (Act). RESULTS: Thirty-three clinical providers and 171 women with breast cancer were included. Improved performance on several QOPI measures was observed for the intervention group compared with the historical control group. CONCLUSION: Meeting the OCM TP requirement through incorporating a technology solution provided an opportunity for quality improvement and preparation for full-scale TP within the OCM. TP delivery was associated with improved performance on select ASCO QOPI measures, which is likely to correspond with improved performance on quality measures within OCM.