bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of calpain in eccentric contraction-induced proteolysis of Ca2+-regulatory proteins and force depression in rat fast-twitch skeletal muscle
Authors: Kanzaki Keita , Watanabe Daiki , Kuratani Mai , Yamada Takashi , Matsunaga Satoshi , Wada Masanobu 
Published: December 2016

The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca2+-regulatory proteins and force production in fast-twitch skeletal muscles. Rat extensor digitorum longus muscles were exposed to 200 repeated ECC in situ and excised immediately [recovery 0 (REC0)] or 3 days [recovery 3 (REC3)] after cessation of ECC. Calpain inhibitor (CI)-treated rats were intraperitoneally injected with MDL-28170 before ECC and during REC3. Tetanic force was markedly reduced at REC0 and remained reduced at REC3. CI treatment ameliorated the ECC-induced force decline but only at REC3. No evidence was found for proteolysis of dihydropyridine receptor (DHPR), junctophilin (JP)1, JP2, ryanodine receptor (RyR), sarcoplasmic reticulum Ca2+-ATPase (SERCA)1a, or junctional face protein-45 at REC0. At REC3, ECC resulted in decreases in DHPR, JP1, JP2, RyR, and SERCA1a. CI treatment prevented the decreases in DHPR, JP1, and JP2, whereas it had little effect on RyR and SERCA1a. These findings suggest that DHPR, JP1, and JP2, but not RyR and SERCA1a, undergo calpain-dependent proteolysis in in vivo muscles subjected to ECC and that impaired function of DHPR and/or JP might cause prolonged force deficits with ECC.NEW & NOTEWORTHY Calpain-dependent proteolysis is one of the contributing factors to muscle damage that occurs with eccentric contraction (ECC). It is unclear, however, whether calpains account for proteolysis of Ca2+-regulatory proteins in in vivo muscles subjected to ECC. Here, we provide evidence that dihydropyridine receptor and junctophilin, but not ryanodine receptor and sarcoplasmic reticulum Ca2+-ATPase, undergo calpain-dependent proteolysis.
Early Effector T Lymphocytes Coexpress Multiple Inhibitory Receptors in Primary Non–Small Cell Lung Cancer
Authors: Tassi Elena , Grazia Giulia , Vegetti Claudia , Bersani Ilaria , Bertolini Giulia , Molla Alessandra , Baldassari Paola , Andriani Francesca , Roz Luca , Sozzi Gabriella , Pastorino Ugo , Mortarini Roberta , Anichini Andrea 
Published: December 2016

Abstract
Clinical efficacy of PD-1/PD-L1 targeting relies upon the reactivation of tumor-specific but functionally impaired PD-1+ T cells present before therapy. Thus, analyzing early-stage primary tumors may reveal the presence of T cells that are not yet functionally impaired. In this study, we report that activated (HLA-DR+) T cells with an effector memory (TEM) profile are enriched in such lesions. Tumor-infiltrating lymphocytes coexpressed PD-1 with the inhibitory receptors TIM-3, CTLA-4, LAG-3, and TIGIT, but also displayed a recently activated, nonexhausted phenotype. We also identified a subset of CD8+PD-1+FOXP3+ T lymphocytes at the earliest phase of functional differentiation after priming, termed “early effector cells” (EEC), which also exhibited an activated nonexhausted phenotype, but was less differentiated and associated with coexpression of multiple inhibitory receptors. In response to autologous tumor, EECs upregulated CD107a, produced IL2 and IFNγ, and were competent for differentiation. The identification of EECs marked by inhibitory receptor expression at tumor sites will enable investigations of early stages of adaptive antitumor immunity, as well as support the rationale for administering immunotherapy in early-stage non–small cell lung cancer. Cancer Res; 77(4); 851–61. ©2016 AACR.
Cytotoxic T Cells and Granzyme B Associated with Improved Colorectal Cancer Survival in a Prospective Cohort of Older Women
Authors: Prizment Anna E. , Vierkant Robert A. , Smyrk Thomas C. , Tillmans Lori S. , Nelson Heather H. , Lynch Charles F. , Pengo Thomas , Thibodeau Stephen N. , Church Timothy R. , Cerhan James R. , Anderson Kristin E. , Limburg Paul J. 
Published: December 2016

AbstractBackground: Host immune response may predict the course of colorectal cancer. We examined the survival of 468 colorectal cancer patients associated with two tumor-infiltrating immune biomarkers, the number of cytotoxic T lymphocytes (CTLs), and the activated CTLs, as reflected by the number of cells expressing granzyme B (GZMB) in the prospective Iowa Women's Health Study.Methods: Using paraffin-embedded tissue samples, we constructed and immunostained tumor microarrays with CD8 (for CTL) and GZMB antibodies. We scored CTL and GZMB densities in tumor epithelial and stromal tissues and also created a composite score for each biomarker (sum of the scores across tissue compartments). Cox regression estimated the HR and 95% confidence intervals (CI) for all-cause and colorectal cancer–specific death associated with each composite score.Results: CTL and GZMB composite scores were positively correlated (r = 0.65) and each biomarker was inversely correlated with stage at diagnosis. Both composite scores were higher in proximal colon tumors and tumors characterized by MSI-high, CIMP-high, or BRAF mutation status. HRs (95% CI) were 0.53 (0.38–0.75; Ptrend = 0.0004) and 0.66 (0.51–0.86; Ptrend = 0.002) for all-cause death, respectively, and 0.30 (0.18–0.51; Ptrend &lt; 0.0001) and 0.41 (0.27–0.63; Ptrend &lt; 0.0001) for colorectal cancer–related death, respectively. Including CTL and GZMB scores simultaneously in the model significantly improved the predictive performance of the models for all-cause and colorectal cancer–related death.Conclusions: Higher tumor infiltration with CTL and GZMB cells is associated with improved all-cause and cancer-specific survival of colorectal cancer patients.Impact: Both the number of CTLs and GZMB appear to be useful prognostic factors in colorectal cancer, irrespective of stage. Cancer Epidemiol Biomarkers Prev; 26(4); 622–31. ©2016 AACR.
The mTORC1/2 Inhibitor AZD8055 Strengthens the Efficiency of the MEK Inhibitor Trametinib to Reduce the Mcl-1/[Bim and Puma] ratio and to Sensitize Ovarian Carcinoma Cells to ABT-737
Authors: Pétigny-Lechartier Cécile , Duboc Charlène , Jebahi Abdelghani , Louis Marie-Hélène , Abeilard Edwige , Denoyelle Christophe , Gauduchon Pascal , Poulain Laurent , Villedieu Marie 
Published: December 2016

AbstractThe identification of novel therapeutic strategies is an important urgent requirement for the clinical management of ovarian cancer, which remains the leading cause of death from gynecologic cancer. Several studies have shown that the antiapoptotic proteins Bcl-xL and Mcl-1, as well as the proapoptotic protein Bim, are key elements to be modulated to kill ovarian cancer cells. Pharmacologic inhibition of Bcl-xL is possible by using BH3-mimetic molecules like ABT-737. However, inhibition of Mcl-1 and/or promotion of its BH3-only partners (including Bim, Puma, and Noxa) remains a challenge that may be achieved by modulating the signaling pathways upstream. This study sought whether AZD8055-induced mTOR inhibition and/or trametinib-induced MEK inhibition could modulate Mcl-1 and its partners to decrease the Mcl-1/BH3-only ratio and thus sensitize various ovarian cancer cell lines to ABT-737. AZD8055 treatment inhibited Mcl-1 and increased Puma expression but did not induce massive apoptosis in combination with ABT-737. In contrast, trametinib, which decreased the Mcl-1/BH3-only protein ratio by upregulating Puma and dephosphorylated active Bim, sensitized IGROV1-R10 and OVCAR3 cells to ABT-737. Adding AZD8055 to trametinib further reduced the Mcl-1/BH3-only protein ratio and triggered apoptosis without ABT-737 in IGROV1-R10 cells. Moreover, the AZD8055/trametinib association highly sensitized all cell lines including SKOV3 to ABT-737, the induced dephosphorylated Bim being crucial in this sensitization. Finally, the three-drug combination was also very efficient when replacing AZD8055 by the pan-Akt inhibitor MK-2206. This study thus proposes original multitargeted strategies and may have important implications for the design of novel approaches for ovarian cancer treatment. Mol Cancer Ther; 16(1); 102–15. ©2016 AACR.
Three-Dimensional Map of Neonatal Arterial Ischemic Stroke Distribution From Early Multimodal Brain Imaging
Authors: Stephan-Otto Christian , Núñez Christian , Arca Gemma , Agut Thais , García-Alix Alfredo 
Published: December 2016

Background and Purpose—
Although neonatal arterial ischemic stroke (NAIS) location has considerable impact on long-term outcome, a map showing spatial distribution of NAIS is lacking. Our aim was to generate this distribution map, based on early magnetic resonance imaging data.

Methods—
Lesions from 34 consecutive neonates with NAIS from a single center were segmented using multimodal magnetic resonance imaging (median age at acquisition =5 days). Lesion masks for all subjects were registered onto a standard neonatal brain and then overlaid to generate a 3D map of NAIS distribution.

Results—
The region posterior to the central sulcus is the most frequently affected in neonates, with 24 of the 34 neonates (71%) showing lesions in this region in at least one hemisphere. Moreover, NAIS frequency is markedly higher in the left hemisphere.

Conclusions—
This is the first report of an NAIS distribution map. Regions posterior to the central sulcus present increased vulnerability. Our findings suggest that motor areas are not as frequently affected as has been previously reported. By contrast, we find high NAIS vulnerability in functional areas related to language. The distribution of ischemic strokes in neonates seems to be different from that seen in adults.
In utero cytomegalovirus infection and development of childhood acute lymphoblastic leukemia
Authors: Francis Stephen Starko , Wallace Amelia D. , Wendt George A. , Li Linlin , Liu Fenyong , Riley Lee W. , Kogan Scott , Walsh Kyle M. , de Smith Adam J. , Dahl Gary V. , Ma Xiaomei , Delwart Eric , Metayer Catherine , Wiemels Joseph L. 
Published: December 2016

Key Points
CMV is prevalent in pretreatment bone marrow from childhood ALL and not in acute myeloid leukemia. In utero infection with CMV is a risk factor for ALL (OR = 3.71, P = .0016) and is more pronounced in Hispanics (OR = 5.90, P = .006).
The societal costs of dementia in Sweden 2012 – relevance and methodological challenges in valuing informal care
Authors: Wimo Anders , Jönsson Linus , Fratiglioni Laura , Sandman Per Olof , Gustavsson Anders , Sköldunger Anders , Johansson Lennarth 
Published: December 2016

Abstract
Background
In this study, we sought to estimate the societal cost of illness in dementia in Sweden in 2012 using different costing approaches to highlight methodological issues.

Methods
We conducted a prevalence-based cost-of-illness study with a societal perspective.

Results
The societal costs of dementia in Sweden in 2012 were SEK 62.9 billion (approximately €7.2 billion, approximately US$9.0 billion) or SEK 398,000 per person with dementia (approximately €45,000, approximately US$57,000). By far the most important cost item is the cost of institutional care: about 60% of the costs. In the sensitivity analysis, different quantification and costing approaches for informal care resulted in a great variation in the total societal cost, ranging from SEK 60 billion (€6.8 billion, US$8.6 billion) to SEK 124 billion (€14.1 billion, US$17.8 billion).

Conclusions
The societal costs of dementia are very high. The cost per person with dementia has decreased somewhat, mainly because of de-institutionalisation. The majority of the costs occur in the social care sector, but the costing of informal care is crucial for the cost estimates.
Virtual reality compared within vivoexposure in the treatment of social anxiety disorder: A three-arm randomised controlled trial
Authors: Bouchard Stéphane , Dumoulin Stéphanie , Robillard Geneviève , Guitard Tanya , Klinger Évelyne , Forget Hélène , Loranger Claudie , Roucaut François Xavier 
Published: December 2016

BackgroundPeople with social anxiety disorder (SAD) fear social interactions and may be reluctant to seek treatments involving exposure to social situations. Social exposure conducted in virtual reality (VR), embedded in individual cognitive–behavioural therapy (CBT), could be an answer.AimsTo show that conducting VR exposure in CBT for SAD is effective and is more practical for therapists than conducting exposurein vivo.MethodParticipants were randomly assigned to either VR exposure (n= 17),in vivoexposure (n= 22) or waiting list (n= 20). Participants in the active arms received individual CBT for 14 weekly sessions and outcome was assessed with questionnaires and a behaviour avoidance test. (Trial registration number ISRCTN99747069.)ResultsImprovements were found on the primary (Liebowitz Social Anxiety Scale) and all five secondary outcome measures in both CBT groups compared with the waiting list. Conducting exposure in VR was more effective at post-treatment thanin vivoon the primary outcome measure and on one secondary measure. Improvements were maintained at the 6-month follow-up. VR was significantly more practical for therapists thanin vivoexposure.ConclusionsUsing VR can be advantageous over standard CBT as a potential solution for treatment avoidance and as an efficient, cost-effective and practical medium of exposure.
Psychosis in autism: Comparison of the features of both conditions in a dually affected cohort
Authors: Larson Felicity V. , Wagner Adam P. , Jones Peter B. , Tantam Digby , Lai Meng-Chuan , Baron-Cohen Simon , Holland Anthony J. 
Published: December 2016

BackgroundThere is limited information on the presentation and characteristics of psychotic illness experienced by people with autism spectrum disorder (ASD).AimsTo describe autistic and psychotic phenomenology in a group of individuals with comorbid ASD and psychosis (ASD–P) and compare this group with populations affected by either, alone.MethodWe studied 116 individuals with ASD–P. We compared features of their ASD with people with ASD and no comorbid psychosis (ASD–NP), and clinical characteristics of psychosis in ASD–P with people with psychosis only.ResultsIndividuals with ASD–P had more diagnoses of atypical psychosis and fewer of schizophrenia compared with individuals with psychosis only. People with ASD–P had fewer stereotyped interests/behaviours compared with those with ASD–NP.ConclusionsOur data show there may be a specific subtype of ASD linked to comorbid psychosis. The results support findings that psychosis in people with ASD is often atypical, particularly regarding affective disturbance.
Naturalist Smellscapes and Environmental Justice
Authors: Hsu Hsuan L. 
Published: December 2016

AbstractThis essay considers naturalist and neonaturalist deployments of smell as a means of mapping uneven and potentially toxic atmospheres in the contexts of Progressive Era urbanization and twentieth-century environmental “slow violence.” After showing how the description of noxious “smellscapes” structures Norris’s Vandover and the Brute (1914), I move on to consider the use of smell in key scenes in the writings of Ann Petry and Helena Viramontes. While environmental justice novels extend Norris’s interest in connections between smell, health, and stratified air, they also explore how these issues intersect with racially uneven geographies in the twentieth century.
Defective adgra2 (gpr124) splicing and function in zebrafish ouchless mutants
Authors: Bostaille Naguissa , Gauquier Anne , Stainier Didier Y. R. , Raible David W. , Vanhollebeke Benoit 
Published: December 2016

ABSTRACT
A hitherto unidentified N-ethyl-N-nitrosourea (ENU)-induced mutation affects dorsal root ganglia (DRG) formation in ouchless mutant zebrafish larvae. In contrast to previous findings assigning the ouchless phenotypes to downregulated sorbs3 transcript levels, this work re-attributes the phenotypes to an essential splice site mutation affecting adgra2 (gpr124) splicing and function. Accordingly, ouchless mutants fail to complement previously characterized adgra2 mutants and exhibit highly penetrant cerebrovascular defects. The aberrantly spliced adgra2 transcript found in ouchless mutants encodes a receptor lacking a single leucine-rich repeat (LRR) within its N-terminus.
Known Unknowns: A Critical Determinant of Confidence and Calibration
Authors: Walters Daniel J. , Fernbach Philip M. , Fox Craig R. , Sloman Steven A. 
Published: December 2016

We propose that an important determinant of judged confidence is the evaluation of evidence that is unknown or missing, and overconfidence is often driven by the neglect of unknowns. We contrast this account with prior research suggesting that overconfidence is due to biased processing of known evidence in favor of a focal hypothesis. In Study 1, we asked participants to list their thoughts as they answered two-alternative forced-choice trivia questions and judged the probability that their answers were correct. Participants who thought more about unknowns were less overconfident. In Studies 2 and 3, we asked participants to list unknowns before assessing their confidence. “Considering the unknowns” reduced overconfidence substantially and was more effective than the classic “consider the alternative” debiasing technique. Moreover, considering the unknowns selectively reduced confidence in domains where participants were overconfident but did not affect confidence in domains where participants were well-calibrated or underconfident. Data, as supplemental material, are available at https://doi.org/10.1287/mnsc.2016.2580 . This paper was accepted by Yuval Rottenstreich, judgment and decision making.
Identity in Charitable Giving
Authors: Kessler Judd B. , Milkman Katherine L. 
Published: December 2016

How does priming identity affect charitable giving? We show that individuals are more likely to donate when a facet of their identity associated with a norm of generosity is primed in an appeal. In large charitable giving field experiments run by the American Red Cross, appeals that prime an individual’s identity as a previous donor to the charity or as a member of a local community generate more donations. The primes are more effective when they highlight a facet of the potential donor’s identity that we hypothesize to be more relevant to his sense of self: priming identity as a previous donor is more effective for more regular donors and priming identity as a local community member is more effective for people in smaller communities. Together, these results elucidate the impact of identity on behavior and demonstrate how identity primes can be implemented in practice to encourage public good provision. This paper was accepted by Uri Gneezy, behavioral economics.
Effectiveness of Reputation in Contracting for Customized Production: Evidence from Online Labor Markets
Authors: Lin Mingfeng , Liu Yong , Viswanathan Siva 
Published: December 2016

This study examines the effects of reputation in the nascent but rapidly growing online labor markets. In these markets, contract winners (vendors) provide clients with customized products such as computer software, business plans, and artistic designs. The products are used primarily for business purposes and require time for production after project-specific contracts are awarded. These characteristics render it unclear whether online reputation will have similar effects as in online retailing, where finished and standardized products are sold for consumption. We analyze field transaction data from a major online labor market. The analyses using matched contract samples and vendor panels consistently show that despite the governing power provided by contracts as well as the litigation and arbitration options, vendors’ online reputation can still be influential on clients. Vendors who have no reputation ratings are less likely to be chosen, and those with higher ratings are more likely to win subsequent bids. Importantly, however, such influences depend on the contract form that is used for a particular transaction—they are significant in output-based contracts but nonsignificant in input-based contracts. Besides extending the research on online reputation to the markets of customized production, this study shows contract form as an important boundary condition for the effectiveness of reputational information. It also provides direct managerial implications for electronic commerce in general and online labor markets in particular. This paper was accepted by Pradeep Chintagunta, marketing.
Dynamic Pricing in Social Networks: The Word-of-Mouth Effect
Authors: Ajorlou Amir , Jadbabaie Ali , Kakhbod Ali 
Published: December 2016

We study the problem of optimal dynamic pricing for a monopolist selling a product to consumers in a social network. In the proposed model, the only means of spread of information about the product is via word-of-mouth communication; consumers’ knowledge of the product is only through friends who already know about the product’s existence. Both buyers and nonbuyers contribute to information diffusion, while buyers are more likely to spread the news about the product. By analyzing the structure of the underlying endogenous dynamic process, we show that the optimal dynamic pricing policy for durable products with zero or negligible marginal cost drops the price to zero infinitely often. The firm uses free offers to attract low-valuation agents and to get them more engaged in the spread. As a result, the firm can reach potential high-valuation consumers in parts of the network that would otherwise remain untouched without the price drops. We provide evidence for this behavior from the smartphone app market, where price histories indicate frequent zero-price sales. Moreover, we show that despite dropping the price to zero infinitely often, the optimal price trajectory does not get trapped near zero. We demonstrate the validity of our results in the face of forward-looking consumers and homophily in word-of-mouth engagement. We further unravel the key role of the product type in the optimality of zero-price sales by showing that the price fluctuations disappear after a finite time for a nondurable product. This paper was accepted by J. Miguel Villas-Boas, marketing.