bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effector gene expression underpins epistasis in a plant fungal disease
Authors: Phan Huyen T.T. , Rybak Kasia , Furuki Eiko , Breen Susan , Solomon Peter S. , Oliver Richard P. , Tan Kar‐Chun 
Published: May 2016

SummaryFungal effector–host sensitivity gene interactions play a key role in determining the outcome of septoria nodorum blotch disease (SNB) caused by Parastagonospora nodorum on wheat. The pathosystem is complex and mediated by interaction of multiple fungal necrotrophic effector–host sensitivity gene systems. Three effector sensitivity gene systems are well characterized in this pathosystem; SnToxA–Tsn1, SnTox1–Snn1 and SnTox3–Snn3. We tested a wheat mapping population that segregated for Snn1 and Snn3 with SN15, an aggressive P. nodorum isolate that produces SnToxA, SnTox1 and SnTox3, to study the inheritance of sensitivity to SnTox1 and SnTox3 and disease susceptibility. Interval quantitative trait locus (QTL) mapping showed that the SnTox1–Snn1 interaction was paramount in SNB development on both seedlings and adult plants. No effect of the SnTox3–Snn3 interaction was observed under SN15 infection. The SnTox3–Snn3 interaction was however, detected in a strain of SN15 in which SnTox1 had been deleted (tox1–6). Gene expression analysis indicates increased SnTox3 expression in tox1–6 compared with SN15. This indicates that the failure to detect the SnTox3–Snn3 interaction in SN15 is due – at least in part – to suppressed expression of SnTox3 mediated by SnTox1. Furthermore, infection of the mapping population with a strain deleted in SnToxA, SnTox1 and SnTox3 (toxa13) unmasked a significant SNB QTL on 2DS where the SnTox2 effector sensitivity gene, Snn2, is located. This QTL was not observed in SN15 and tox1–6 infections and thus suggesting that SnToxA and/or SnTox3 were epistatic. Additional QTLs responding to SNB and effectors sensitivity were detected on 2AS1 and 3AL.
Evaluation of a genetic assay for canine transmissible venereal tumour diagnosis in Brazil
Authors: Castro K. F. , Strakova A. , Tinucci‐Costa M. , Murchison E. P. 
Published: May 2016

AbstractThe canine transmissible venereal tumour (CTVT) is a transmissible cancer that is spread between dogs by the allogeneic transfer of living cancer cells. The infectious agents in CTVT are the living cancer cells themselves, which are transmitted between dogs during coitus. CTVT first arose several thousand years ago and the disease has a global distribution and is frequently observed in dogs from Brazil. We evaluated the utility of a LINE‐MYC quantitative polymerase chain reaction for diagnosis of CTVT cases in Brazil. Our analysis indicated that the LINE‐MYC rearrangement was detectable in all CTVT samples but not in their corresponding hosts. This genetic assay proves to be a useful tool for providing a definitive molecular diagnosis of CTVT, which presents with varying degrees of aggressiveness and invasiveness in different host dogs and can therefore be a diagnostic challenge in some specific cases.
Identification of occult micrometastases and isolated tumour cells within regional lymph nodes of previously diagnosed non‐metastatic (stage 0) canine carcinomas
Authors: Casey K. M. , Steffey M. A. , Affolter V. K. 
Published: May 2016

AbstractMetastatic dissemination of carcinomas to lymph nodes impacts prognosis and treatment recommendations in human and veterinary medicine. Routine histopathologic evaluation of regional lymph nodes involves haematoxylin and eosin (H&E) staining to identify intra‐nodal neoplastic cells; however, identification of small volume metastases (micrometastases and individual tumour cells) may be missed without the aid of immunohistochemistry or additional step‐sections. The aim of this study was to identify occult carcinoma metastases in previously diagnosed non‐metastatic lymph nodes using step‐sections and pancytokeratin (panCK) immunohistochemistry. Samples from 20 regional lymph nodes diagnosed as non‐metastatic were serially sectioned and evaluated with panCK. Of these, 25% (n = 5) contained micrometastases (n = 1) or isolated tumour cells (n = 4). This study demonstrates the increased efficacy of serial step‐sections combined with panCK immunohistochemistry to identify small volume metastases in regional lymph nodes. The prognostic significance of micrometastases and isolated tumour cells in regional lymph nodes warrants further investigation in veterinary medicine.
Retrospective comparison of three doses of metronomic chlorambucil for tolerability and efficacy in dogs with spontaneous cancer
Authors: Custead M. R. , Weng H.Y. , Childress M. O. 
Published: May 2016

AbstractThe study hypothesis is that higher doses of metronomic (low‐dose) chlorambucil will improve outcome without significantly worsening adverse events (AE). Retrospectively, 88 dogs were screened to assess for tolerability and response to chlorambucil utilizing retrospective and prospective data sets, comparing metronomic oral daily doses 4, 6 and 8 mg m2. There were 78 and 70 dogs in the tolerability and efficacy portions, respectively. The severity of gastrointestinal (GI) AE was significantly worse, and time to development of GI events was significantly shorter at 6 mg m2 than at 4 mg m2 (both P < 0.001). Chlorambucil was discontinued earlier in the dogs treated at the 6 mg m2 doses than in the dogs treated at 4 mg m2 (P = 0.015). Thrombocytopenia occurred significantly earlier at 8 mg m2 than at 4 mg m2 (P = 0.017). Higher doses of metronomic (low‐dose) chlorambucil did not provide improved responses and were associated with more AE.
Self-Mobilization Using a Foam Roller Versus a Roller Massager: Which Is More Effective for Increasing Hamstrings Flexibility?
Authors: DeBruyne Danielle M. , Dewhurst Marina M. , Fischer Katelyn M. , Wojtanowski Michael S. , Durall Chris 
Published: May 2016

Clinical Scenario:Increasing the length of the muscle–tendon unit may prevent musculotendinous injury. Various methods have been proposed to increase muscle–tendon flexibility, including self-mobilization using foam rollers or roller massagers, although the effectiveness of these devices is uncertain. This review was conducted to determine if the use of foam rollers or roller massagers to improve hamstrings flexibility is supported by moderate- to high-quality evidence.Clinical Question:Are foam rollers or roller massagers effective for increasing hamstrings flexibility in asymptomatic physically active adults?Summary of Key Findings:The literature was searched for studies on the effects of using foam rollers or roller massagers to increase hamstrings flexibility in asymptomatic physically active adults. Four randomized controlled trials were included; 2 studies provided level 2 or 3 evidence regarding foam rollers and 2 studies provided level 2 or 3 evidence regarding roller massagers. Both roller-massager studies reported increases in hamstrings flexibility after treatment. Data from the foam-roller studies did not demonstrate a statistically significant increase in hamstrings flexibility, but 1 study did demonstrate a strong effect size.Clinical Bottom Line:The reviewed moderate-quality studies support the use of roller massagers but provide limited evidence on the effectiveness of foam rolling to increase hamstrings flexibility in asymptomatic physically active adults. Flexibility gains may be improved by a longer duration of treatment and administration by a trained therapist. Gains appear to decline rapidly postrolling. Neither device has been shown to confer a therapeutic benefit superior to static stretching, and the effectiveness of these devices for preventing injury is unknown.Strength of Recommendation:Grade B evidence supports the use of roller massagers to increase hamstrings flexibility in asymptomatic physically active adults.
Urinary Tract Physiological Conditions Promote Ciprofloxacin Resistance in Low-Level-Quinolone-Resistant Escherichia coli
Authors: Martín-Gutiérrez Guillermo , Rodríguez-Beltrán Jerónimo , Rodríguez-Martínez José Manuel , Costas Coloma , Aznar Javier , Pascual Álvaro , Blázquez Jesús 
Published: May 2016

ABSTRACT

Escherichia coli
isolates carrying chromosomally encoded low-level-quinolone-resistant (LLQR) determinants are frequently found in urinary tract infections (UTIs). LLQR mutations are considered the first step in the evolutionary pathway producing high-level fluoroquinolone resistance. Therefore, their evolution and dissemination might influence the outcome of fluoroquinolone treatments of UTI. Previous studies support the notion that low urine pH decreases susceptibility to ciprofloxacin (CIP) in
E. coli
. However, the effect of the urinary tract physiological parameters on the activity of ciprofloxacin against LLQR
E. coli
strains has received little attention. We have studied the activity of ciprofloxacin under physiological urinary tract conditions against a set of well-characterized isogenic
E. coli
derivatives carrying the most prevalent chromosomal mutations (Δ
marR
,
gyrA
-S83L,
gyrA
-D87N, and
parC
-S80R and some combinations). The results presented here demonstrate that all the LLQR strains studied became resistant to ciprofloxacin (according to CLSI guidelines) under physiological conditions whereas the control strain lacking LLQR mutations did not. Moreover, the survival of some LLQR
E. coli
variants increased up to 100-fold after challenge with a high concentration of ciprofloxacin under UTI conditions compared to the results seen with Mueller-Hinton broth. These selective conditions could explain the high prevalence of LLQR mutations in
E. coli
. Furthermore, our data strongly suggest that recommended methods for MIC determination produce poor estimations of CIP activity against LLQR
E. coli
in UTIs.
High dose of phytase on apparent and standardized total tract digestibility of phosphorus and apparent total tract digestibility of calcium in canola meals from Brassica napus black and Brassica juncea yellow fed to growing pigs
Authors: Adhikari P.A. , Heo J.M. , Nyachoti C.M. 
Published: May 2016

A total of 42 barrows weighing 19.8 ± 1.22 kg were fed seven diets to give six replicates per treatment. The experiment was conducted in a factorial arrangement with factors being (1) two canola meals (CM) types and (2) three phytase levels (0, 500, and 2500 FTU kg−1). The basal endogenous phosphorus (P) losses and standardized total tract digestibility (STTD) was calculated using the P-free method. There was no effect of CM types on feed intake and fecal P output, but an interaction effect was observed for P intake (CM × phytase; P < 0.05). Supplementation of phytase (2500 FTU kg−1) reduced (P < 0.001) fecal P output (g d−1), and the output was reduced by 58% in Brassica napus black (BNB) and 64% in Brassica juncea yellow (BJY) diets. Supplementation of phytase improved (P < 0.001) both apparent total tract digestibility (ATTD) and STTD of P in both BNB and BJY, regardless of dose. The basal endogenous P loss (EPL) was determined to be 111.28 ± 35.09 mg kg−1 of dry matter intake (DMI). There was no further improvement in STTD of P when phytase was increased from 500 to 2500 FTU kg−1 in both CM types. The ATTD of calcium (Ca) was increased (P < 0.001) in BNB and BJY when phytase was supplemented at 500 and 2500 FTU kg−1. The results, therefore, indicate that supplementation of phytase at 500 FTU kg−1 improved both ATTD and STTD of P in two CM types, but a super dose of 2500 FTU kg−1 had no additional benefit. Similarly, ATTD of Ca was increased when phytase was supplemented at 500 FTU kg−1 without further improvement at 2500 FTU kg−1.
Tablet-Based Activity Schedule in Mainstream Environment for Children with Autism and Children with ID
Authors: Fage Charles , Pommereau Léonard , Consel Charles , Balland Emilie , Sauzéon Hélène 
Published: May 2016

Including children with autism spectrum disorders (ASD) in mainstream environments creates a need for new interventions whose efficacy must be assessed in situ. This article presents a tablet-based application for activity schedules that has been designed following a participatory design approach involving mainstream teachers, special education teachers, and school aides. This application addresses two domains of activities: classroom routines and verbal communications.
We assessed the efficiency of our application with two overlapping user studies in mainstream inclusion, sharing a group of children with ASD. The first experiment involved 10 children with ASD, where five children were equipped with our tabled-based application and five were not equipped. We show that (1) the use of the application is rapidly self-initiated (after 2 months for almost all the participants) and (2) the tablet-supported routines are better performed after 3 months of intervention. The second experiment involved 10 children equipped with our application; it shared the data collected for the five children with ASD and compared them with data collected for five children with intellectual disability (ID).
We show that (1) children with ID are not autonomous in the use of the application at the end of the intervention, (2) both groups exhibited the same benefits on classroom routines, and (3) children with ID improve significantly less their performance on verbal communication routines. These results are discussed in relation with our design principles. Importantly, the inclusion of a group with another neurodevelopmental condition provided insights about the applicability of these principles beyond the target population of children with ASD.
Second-Generation HSP90 Inhibitor Onalespib Blocks mRNA Splicing of Androgen Receptor Variant 7 in Prostate Cancer Cells
Authors: Ferraldeschi Roberta , Welti Jonathan , Powers Marissa V. , Yuan Wei , Smyth Tomoko , Seed George , Riisnaes Ruth , Hedayat Somaieh , Wang Hannah , Crespo Mateus , Nava Rodrigues Daniel , Figueiredo Ines , Miranda Susana , Carreira Suzanne , Lyons John F. , Sharp Swee , Plymate Stephen R. , Attard Gerhardt , Wallis Nicola , Workman Paul , de Bono Johann S. 
Published: May 2016

Abstract
Resistance to available hormone therapies in prostate cancer has been associated with alternative splicing of androgen receptor (AR) and specifically, the expression of truncated and constitutively active AR variant 7 (AR-V7). The transcriptional activity of steroid receptors, including AR, is dependent on interactions with the HSP90 chaperone machinery, but it is unclear whether HSP90 modulates the activity or expression of AR variants. Here, we investigated the effects of HSP90 inhibition on AR-V7 in prostate cancer cell lines endogenously expressing this variant. We demonstrate that AR-V7 and full-length AR (AR-FL) were depleted upon inhibition of HSP90. However, the mechanisms underlying AR-V7 depletion differed from those for AR-FL. Whereas HSP90 inhibition destabilized AR-FL and induced its proteasomal degradation, AR-V7 protein exhibited higher stability than AR-FL and did not require HSP90 chaperone activity. Instead, HSP90 inhibition resulted in the reduction of AR-V7 mRNA levels but did not affect total AR transcript levels, indicating that HSP90 inhibition disrupted AR-V7 splicing. Bioinformatic analyses of transcriptome-wide RNA sequencing data confirmed that the second-generation HSP90 inhibitor onalespib altered the splicing of at least 557 genes in prostate cancer cells, including AR. These findings indicate that the effects of HSP90 inhibition on mRNA splicing may prove beneficial in prostate cancers expressing AR-V7, supporting further clinical investigation of HSP90 inhibitors in malignancies no longer responsive to androgen deprivation. Cancer Res; 76(9); 2731–42. ©2016 AACR.
Feasibility of Telomerase-Specific Adoptive T-cell Therapy for B-cell Chronic Lymphocytic Leukemia and Solid Malignancies
Authors: Sandri Sara , Bobisse Sara , Moxley Kelly , Lamolinara Alessia , De Sanctis Francesco , Boschi Federico , Sbarbati Andrea , Fracasso Giulio , Ferrarini Giovanna , Hendriks Rudi W. , Cavallini Chiara , Scupoli Maria Teresa , Sartoris Silvia , Iezzi Manuela , Nishimura Michael I. , Bronte Vincenzo , Ugel Stefano 
Published: May 2016

Abstract
Telomerase (TERT) is overexpressed in 80% to 90% of primary tumors and contributes to sustaining the transformed phenotype. The identification of several TERT epitopes in tumor cells has elevated the status of TERT as a potential universal target for selective and broad adoptive immunotherapy. TERT-specific cytotoxic T lymphocytes (CTL) have been detected in the peripheral blood of B-cell chronic lymphocytic leukemia (B-CLL) patients, but display low functional avidity, which limits their clinical utility in adoptive cell transfer approaches. To overcome this key obstacle hindering effective immunotherapy, we isolated an HLA-A2–restricted T-cell receptor (TCR) with high avidity for human TERT from vaccinated HLA-A*0201 transgenic mice. Using several relevant humanized mouse models, we demonstrate that TCR-transduced T cells were able to control human B-CLL progression in vivo and limited tumor growth in several human, solid transplantable cancers. TERT-based adoptive immunotherapy selectively eliminated tumor cells, failed to trigger a self–MHC-restricted fratricide of T cells, and was associated with toxicity against mature granulocytes, but not toward human hematopoietic progenitors in humanized immune reconstituted mice. These data support the feasibility of TERT-based adoptive immunotherapy in clinical oncology, highlighting, for the first time, the possibility of utilizing a high-avidity TCR specific for human TERT. Cancer Res; 76(9); 2540–51. ©2016 AACR.
Stromal-Based Signatures for the Classification of Gastric Cancer
Authors: Uhlik Mark T. , Liu Jiangang , Falcon Beverly L. , Iyer Seema , Stewart Julie , Celikkaya Hilal , O'Mahony Marguerita , Sevinsky Christopher , Lowes Christina , Douglass Larry , Jeffries Cynthia , Bodenmiller Diane , Chintharlapalli Sudhakar , Fischl Anthony , Gerald Damien , Xue Qi , Lee Jee-yun , Santamaria-Pang Alberto , Al-Kofahi Yousef , Sui Yunxia , Desai Keyur , Doman Thompson , Aggarwal Amit , Carter Julia H. , Pytowski Bronislaw , Jaminet Shou-ching , Ginty Fiona , Nasir Aejaz , Nagy Janice A. , Dvorak Harold F. , Benjamin Laura E. 
Published: May 2016

Abstract
Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, we integrated a mouse model of stromal activation and gastric cancer genomic information to identify gene expression signatures that may inform treatment strategies. We generated a mouse model in which VEGF-A is expressed via adenovirus, enabling a stromal response marked by immune infiltration and angiogenesis at the injection site, and identified distinct stromal gene expression signatures. With these data, we designed multiplexed IHC assays that were applied to human primary gastric tumors and classified each tumor to a dominant stromal phenotype representative of the vascular and immune diversity found in gastric cancer. We also refined the stromal gene signatures and explored their relation to the dominant patient phenotypes identified by recent large-scale studies of gastric cancer genomics (The Cancer Genome Atlas and Asian Cancer Research Group), revealing four distinct stromal phenotypes. Collectively, these findings suggest that a genomics-based systems approach focused on the tumor stroma can be used to discover putative predictive biomarkers of treatment response, especially to antiangiogenesis agents and immunotherapy, thus offering an opportunity to improve patient stratification. Cancer Res; 76(9); 2573–86. ©2016 AACR.
The Effects of Residential Segregation and Neighborhood Characteristics on Surgery and Survival in Patients with Early-Stage Non–Small Cell Lung Cancer
Authors: Johnson Asal M. , Johnson Allen , Hines Robert B. , Bayakly Rana 
Published: May 2016

Abstract
Background: Although the negative effects of lower socioeconomic status on non–small cell lung cancer (NSCLC) treatment and survival have been widely studied, the impact of residential segregation on prognosis and the receipt of treatment has yet to be determined.
Methods: This is a retrospective, cohort study of NSCLC patients in Georgia (2000–2009; n = 8,322) using data from the Georgia Comprehensive Cancer Registry. The effects of segregation, economic deprivation, and combined segregation/deprivation on the odds of receiving surgery were examined in separate multilevel models. To determine the association for the exposures of interest on the risk of death for different racial groups, separate multilevel survival models were conducted for black and white patients.
Results: Living in areas with the highest [AOR = 0.35, 95% confidence interval (CI), 0.19–0.64] and second highest (AOR = 0.37, 95% CI, 0.20–0.68) levels of segregation was associated with decreased odds of receipt of surgery. Black patients living in areas with high residential segregation and high economic deprivation were 31% (95% CI, 1.04–1.66) more likely to die, even after surgery was controlled for. For white patients, economic deprivation was associated with decreased odds of surgery but not survival. Segregation had no effect.
Conclusion: Our findings suggest how black and white individuals experience segregation and area-level poverty is likely different leading to differences in adverse health outcomes.
Impact: Identifying neighborhood characteristics impacting health outcomes within different racial groups could help reduce health disparities across racial groups by implementing targeted policies and interventions. Cancer Epidemiol Biomarkers Prev; 25(5); 750–8. ©2016 AACR.
MENA Promotes Tumor-Intrinsic Metastasis through ECM Remodeling and Haptotaxis
Authors: Santiago-Medina Miguel , Yang Jing 
Published: May 2016

Abstract
Summary: Oudin and colleagues report a novel and specific function of MENA in mediating directional migration of breast cancer cells toward a fibronectin gradient of increasing concentration. This MENA-mediated haptotactic response depends on the binding of MENA to the α5β1 integrin receptor, adhesion protein signaling, and fibronectin fibrillogenesis. Cancer Discov; 6(5); 474–6. ©2016 AACR.
See related article by Oudin et al., p. 516.
PD-1 Shapes B Cells as Evildoers in the Tumor Microenvironment
Authors: Ren Zhenhua , Peng Hua , Fu Yang-Xin 
Published: May 2016

Abstract
Summary: Protumorigenic PD-1hi B cells, induced in hepatocellular carcinoma, suppress tumor-specific T-cell response via IL10-dependent pathways upon PD-1/PD-L1 interaction. Anti–PD-1 or anti–PD-L1 antibodies may function not only through blocking the PD-1 coinhibitory pathway in T cells but also via abolishing the suppressive function of regulatory B cells. Cancer Discov; 6(5); 477–8. ©2016 AACR.
See related article by Xiao et al., p. 546.