bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic Profiling of the Tumor Microenvironment Reveals Distinct Subgroups of Clear Cell Renal Cell Cancer: Data from a Randomized Phase III Trial
Authors: Hakimi A. Ari , Voss Martin H. , Kuo Fengshen , Sanchez Alejandro , Liu Ming , Nixon Briana G. , Vuong Lynda , Ostrovnaya Irina , Chen Ying-Bei , Reuter Victor , Riaz Nadeem , Cheng Yuan , Patel Parul , Marker Mahtab , Reising Albert , Li Ming O. , Chan Timothy A. , Motzer Robert J. 
Published: January 2019

Abstract

Metastasis remains the main reason for renal cell carcinoma (RCC)–associated mortality. Tyrosine kinase inhibitors (TKI) impart clinical benefit for most patients with RCC, but the determinants of response are poorly understood. We report an integrated genomic and transcriptomic analysis of patients with metastatic clear cell RCC (ccRCC) treated with TKI therapy and identify predictors of response. Patients in the COMPARZ phase III trial received first-line sunitinib or pazopanib with comparable efficacy. RNA-based analyses revealed four distinct molecular subgroups associated with response and survival. Characterization of these subgroups identified mutation profiles, angiogenesis, and macrophage infiltration programs to be powerful predictors of outcome with TKI therapy. Notably, predictors differed by the type of TKI received. Our study emphasizes the clinical significance of angiogenesis and immune tumor microenvironment and suggests that the critical effects its various aspects have on TKI efficacy vary by agent. This has broad implications for optimizing precision treatment of RCC.

Significance:
The determinants of response to TKI therapy in metastatic ccRCC remain unknown. Our study demonstrates that key angiogenic and immune profiles of the tumor microenvironment may affect TKI response. These findings have the potential to inform treatment personalization in patients with RCC.
This article is highlighted in the In This Issue feature, p. 453
Is my World Getting Smaller? The Challenges of Living with Vision Loss
Authors: Berger Sue 
Published: January 2019

Introduction Vision loss influences both basic and instrumental activities of daily living. There is limited information, however, on the relationship between vision loss and leisure activities. The research presented here was part of a larger study that aimed to understand the importance of participation in leisure activities for those with vision loss. This article focuses on one key theme that emerged from the data: the challenge of engaging in leisure activities outside the home for older adults with vision loss. Methods Semistructured interviews and participant observation were used to collect data from 26 adults aged 70 years and older with vision loss. Only those who perceived themselves to be in good or excellent overall health, separate from vision loss, were included. Results Themes that emerged related to limited leisure activities outside the home included both personal and environmental factors, such as challenging physical environments, struggling to “get there,” feelings of vulnerability, having decreased energy, and lacking assertiveness. Discussion The results indicated that vision loss is a key factor that limits one's ability to engage in out-of-home activities. There is a mismatch between environmental and personal factors that prevents participation in many activities. Although it appears that the participants chose not to engage in leisure activities outside the home because the activities were not within their competence, it is clear that these decisions were neither easy nor desirable. Implications for practitioners Therapists who provide services to older adults with vision loss should work with their clients to explore ways to facilitate participation in leisure activities in the community. Advocating for features that increase access and participation, addressing safety, exploring ways to conserve energy, and practicing assertive communication are all important components of a comprehensive vision rehabilitation program.
Ability or Access-ability: Differential Item Functioning of Items on Alternate Performance-Based Assessment Tests for Students with Visual Impairments
Authors: Zebehazy Kim T. , Zigmond Naomi , Zimmerman George J. 
Published: January 2019

Introduction This study investigated differential item functioning (DIF) of test items on Pennsylvania's Alternate System of Assessment (PASA) for students with visual impairments and severe cognitive disabilities and what the reasons for the differences may be. Methods The Wilcoxon signed ranks test was used to analyze differences in the scores of the students with visual impairments and severe cognitive disabilities who took the Grade 3–4 or 7–8 Level A PASA compared to matched peers without visual impairments. The students with visual impairments were analyzed as a group and by level of functional vision. Logical analyses of videotaped assessments of the students with visual impairments were conducted to identify potential sources of DIF. Results Among the functional vision groups, 17 instances in reading and 22 instances in math were flagged for DIF, with 14 skills in reading and 13 in math emerging as harder for students with visual impairments. The types of items that were significantly different included those involving money, matching, and selecting the smallest. Potential reasons for the differences included students needing a better orientation to test materials; the influence of lucky guesses based on distractor characteristics; and the influence of accommodations, such as the substitution of objects. Discussion The results demonstrate the complexity and importance of evaluating the validity of alternate performance-based assessments for students with visual impairments and severe cognitive disabilities. The themes that emerged suggest the need to structure alternate assessment tasks for consistent orientation to materials and to consider closely how accommodations affect the difficulty of the tasks. Implications for practitioners Practitioners should consider how the reading progression for their students with visual impairments and severe cognitive disabilities is related to alternate standards and the instruction that is in place to learn concepts that were missed incidentally. Practitioners can help improve alternate assessments by communicating with their states about the types of tasks that are difficult to accommodate in their current format or by requesting guidance in making meaningful accommodations that maintain the intent of the items.
Instruction in Specialized Braille Codes, Abacus, and Tactile Graphics at Universities in the United States and Canada
Authors: Rosenblum L. Penny , Smith Derrick 
Published: January 2019

Introduction This study gathered data on methods and materials that are used to teach the Nemeth braille code, computer braille, foreign-language braille, and music braille in 26 university programs in the United States and Canada that prepare teachers of students with visual impairments. Information about instruction in the abacus and the preparation of tactile graphics was also gathered. Methods A faculty representative from each university completed a 39-question online demographic survey during fall 2011. Frequency counts for each item were tabulated, and comments were reviewed and categorized. Results All 26 university programs provided instruction in the Nemeth braille code. Most also provided introductory information on foreign-language braille, computer braille, and music braille. There was a high rate of consistency across the programs in what constituted a braille error. The university programs required students to prepare tactile graphics and learn computation on the abacus. The delivery of courses through a hybrid model was most common. Discussion University programs are providing instruction in the Nemeth braille code, though there is variability in the topics that are covered, the books that are used, and the assignments that are required. Most university programs are also exposing their preservice students to specialized braille codes and are teaching them to produce tactile graphics and to perform computations on the abacus. Future studies are needed to look at the quality of instruction and, if the amount of instruction in the different topics is sufficient, to prepare future teachers of students with visual impairments adequately. Implications for practitioners Data gathered from this study will assist university programs to evaluate the content of their courses on the topics that were studied. Adjustment in the content of courses may result, which may subsequently affect the skill set of practitioners as they complete university preparation.
Sexual Activity of Young Adults who are Visually Impaired and the Need for Effective Sex Education
Authors: Kelly Stacy M. , Kapperman Gaylen 
Published: January 2019

Introduction Little research has been reported on all aspects of sexuality as it pertains to individuals with visual impairments. This article analyzes data on the sexual experiences of young adults who are visually impaired and young adults without disabilities. Methods The authors conducted a secondary analysis of the National Longitudinal Transition Study-2 (NLTS2) federal database and assessed a nationally representative sample of transition-aged young adults with visual impairments. During the same period as the NLTS2, identical survey questions were asked of young adults without disabilities who participated in survey research by the Centers for Disease Control and Prevention (CDC). The CDC survey sample included young adults who were two to three years younger than the participants in the NLTS2 sample. The descriptive analysis presents estimates of the sexual activity and use of contraception by both samples. Results Of the transition-aged young adults with visual impairments, 57% reported having sexual intercourse, and of the transition-aged young adults without disabilities, 65% reported having sexual intercourse. Likewise, nearly 40% of the young adults with visual impairments and approximately 50% of those without disabilities reported having had sexual intercourse in the three months before the survey. The use of condoms was also similar (64% of those with visual impairments and 54% of those without disabilities) even though the use of contraceptives other than condoms varied between the samples. Discussion The transition-aged young adults with visual impairments reported having similar rates of sexual experiences as their sighted counterparts, except two to three years later. Implications for Practitioners The researchers concluded that there is a need to provide effective instruction in sexual health that incorporates meaningful methods and materials that are designed specifically to meet the unique needs of young adults who are visually impaired.
Assistive Technology Competencies for Teachers of Students with Visual Impairments: A National Study
Authors: Zhou Li , Ajuwon Paul M. , Smith Derrick W. , Griffin-Shirley Nora , Parker Amy T. , Okungu Phoebe 
Published: January 2019

Introduction For practicing teachers of students with visual impairments, assistive technology has assumed an important role in the education of their students’ assessment and learning of content. Little research has addressed this area; therefore, the purpose of the study presented here was to identify the teachers’ self-reported possession of knowledge of and skills in assistive technology. Method The participants completed an online survey rating their level of expertise in assistive technology. The researchers used descriptive statistics and Pearson r correlation coefficients. Results In total, 840 teachers of students with visual impairments in the United States, Palau, and the Virgin Islands completed an online survey to identify their perceived level of mastery of assistive technology competencies. Regarding the participants’ confidence in teaching and supporting the use of assistive technology for students with visual impairments, 40.7% of the participants were confident or very confident, whereas 59.3% reported no to some confidence. In addition, the younger teachers were relatively more confident in teaching assistive technology than were the older teachers. Specifically, the participants felt the least confident with the foundations domain of assistive technology and the most confident with collaboration. Discussion The results describe teachers’ self-perceptions and pinpoint areas for further intervention and dialogue. Personnel preparation programs and in-service training programs can concentrate on these specific areas of assistive technology to improve teachers’ levels of confidence with assistive technology domains. Collaborating to create systemic, national interventions is crucial for improving educational and vocational outcomes for all individuals with visual impairments. Implications for practitioners First, given the findings of the study, it is recommended that all university programs develop a course on assistive technology, as well as embed assistive technology competencies in their training curricula. Second, research is needed to explore further what universities are currently doing to address assistive technology in their curricula. Finally, professional organizations should provide ongoing in-service training in assistive technology for practicing teachers of students with visual impairments.
The Abacus: Teachers’ Preparation and Beliefs about their Abacus Preservice Preparation
Authors: Rosenblum L. Penny , Hong Sunggye , Amato Sheila 
Published: January 2019

Introduction This article reports on a study of 196 teachers who shared their experiences and opinions related to how they were taught to use the Cranmer abacus. Methods In February and March 2012, the participants completed an online survey to gather information about their preparation in using and beliefs about computation with the Cranmer abacus. Results The participants resided in both the United States and Canada and had various years of experience. The majority (n = 112) reported learning computation with an abacus in their personnel preparation programs. The participants rated their level of agreement with belief statements. Statements with the highest level of agreement included one that indicated that when sighted individuals use pencil and paper for computation, an individual with a visual impairment should be allowed to use an abacus, and another that an abacus is an accessible and inexpensive tool. Discussion The self-report data from 196 participants indicated that computation with an abacus is taught in university programs, although there is variability in what computational skills are taught and what methods are used. There was a higher level of agreement with statements that implied the positive attributes of using an abacus for computation than with those that implied negative attributes (for example, the abacus is obsolete). Implications for practitioners University preparation programs are continuing to teach some level of abacus computation skills to their students. It is not clear if the level of instruction is adequate. Further studies are warranted that examine what pre- and in-service teachers of students with visual impairments are learning and how they are learning in their university preparation programs and through other methods.
Molecular and cytogenetic analysis of infertile Hakka men with azoospermia and severe oligozoospermia in southern China
Authors: Zhao Pingsen , Gu Xiaodong , Wu Heming , Deng Xunwei 
Published: January 2019

Objective To determine the prevalence of chromosome abnormalities and azoospermia factor (AZF) microdeletions in Hakka men with infertility in southern China. Methods Hakka male patients, who received clinical counselling for infertility between August 2016 and October 2017, and fertile male controls, were enrolled into this retrospective study. Patients diagnosed with infertility and controls underwent cytogenetic analysis by standard G-banding; AZF microdeletions were examined by multiplex polymerase chain reaction and capillary electrophoresis. Results Out of 918 male patients who received fertility counselling, 57 were diagnosed with infertility due to azoospermia or severe oligozoospermia. Of these infertile patients, 22.81% (13/57) carried chromosome abnormalities, with 47, XXY being the most common abnormal karyotype. In addition, 36.84% (21/57) presented with Y chromosome microdeletions, most frequently in the complete AZFc and partial AZFc region. Duplication of the AZFc region was found in three patients. No AZF microdeletions were found in 60 fertile male controls. Conclusion The high AZF microdeletion frequency in the current Hakka population suggests that AZF microdeletion analysis is essential in fertility screening, and combined with cytogenetic analysis, may influence the choice of assisted reproductive techniques and reduce the risk of inherited genetic disease.
Trait Conscientiousness predicts rate of longitudinal SDMT decline in multiple sclerosis
Authors: Fuchs Tom A , Wojcik Curtis , Wilding Gregory E , Pol Jeta , Dwyer Michael G , Weinstock-Guttman Bianca , Zivadinov Robert , Benedict Ralph HB 
Published: January 2019

Background: Many people with multiple sclerosis (MS) exhibit cognitive decline over several years. Baseline differences may put people at greater risk for such decline. Objective: To characterize rates of longitudinal cognitive decline and investigate baseline clinical predictors. Methods: We report a retrospective analysis of 531 MS patients whose data were gleaned from a multi-study database, aggregated over 16 years. Linear mixed effects modeling was applied to estimate the average rate of decline on Symbol Digit Modalities Test (SDMT) performance and to predict rates of decline using baseline clinical variables. Results: Participants exhibited an average estimated decline of 0.22 SDMT raw-score points/year (95% confidence interval (CI) (−0.32, −0.12)). We observed a significant main effect of time from baseline ( t = −2.78, p = 0.006), test form ( t = 2.13, p = 0.034), disease course ( t = 2.91, p = 0.004), age ( t = −2.76, p = 0.006), sex ( t = −2.71, p = 0.007), subjective cognitive impairment ( t = −2.00, p = 0.046), premorbid verbal intelligence ( t = 5.14, p < 0.001), and trait Conscientiousness ( t = 2.69, p = 0.008). A significant interaction emerged for Conscientiousness and time from baseline ( t = 2.57, p = 0.011). Conclusion: Higher baseline trait Conscientiousness predicts slower rates of longitudinal cognitive decline in MS. This relationship, the average rate of decline, and practice effects can inform future research and clinical treatment decisions.
Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with β-thalassemia
Authors: Piga Antonio , Perrotta Silverio , Gamberini Maria Rita , Voskaridou Ersi , Melpignano Angela , Filosa Aldo , Caruso Vincenzo , Pietrangelo Antonello , Longo Filomena , Tartaglione Immacolata , Borgna-Pignatti Caterina , Zhang Xiaosha , Laadem Abderrahmane , Sherman Matthew L. , Attie Kenneth M. 
Published: January 2019

Abstractβ-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with β-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non–transfusion dependent (mean hemoglobin, &lt;10.0 g/dL; &lt;4 red blood cell [RBC] units transfused per 8 weeks), and 31 were transfusion dependent (≥4 RBC units per 8 weeks). Patients received 0.2 to 1.25 mg/kg luspatercept subcutaneously every 21 days for ≥5 cycles (dose-finding stage) and 0.8 to 1.25 mg/kg (expansion cohort and 5-year extension). The primary end point was erythroid response, defined as hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 consecutive days (without RBC transfusions) for non–transfusion-dependent patients or RBC transfusion burden reduction ≥20% over a 12-week period vs the 12 weeks before treatment for transfusion-dependent patients. Eighteen non–transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase ≥1.5 g/dL over ≥14 days vs baseline. Twenty-six (81%) transfusion-dependent patients achieved ≥20% reduction in RBC transfusion burden. The most common grade 1 to 2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of β-thalassemia patients receiving luspatercept had hemoglobin or transfusion burden improvements. These findings support a randomized clinical trial to assess efficacy and safety. This study was registered at www.clinicaltrials.gov as #NCT01749540 and #NCT02268409.
ARNTL hypermethylation promotes tumorigenesis and inhibits cisplatin sensitivity by activating CDK5 transcription in nasopharyngeal carcinoma
Authors: Peng Hao , Zhang Jian , Zhang Pan-Pan , Chen Lei , Tang Ling-Long , Yang Xiao-Jing , He Qing-Mei , Wen Xin , Sun Ying , Liu Na , Li Ying-Qin , Ma Jun 
Published: January 2019

Abstract
Background
Increasing evidence support an important role for DNA methylation in nasopharyngeal carcinoma (NPC). Here, we explored the role of circadian clock gene Aryl Hydrocarbon Receptor Nuclear Translocator-Like (ARNTL) methylation in NPC.

Methods
We employed bisulfite pyrosequencing to determine the epigenetic change of ARNTL in NPC cell lines and tissues. ARNTL mRNA and protein expression in cell lines and tissues were detected by real-time PCR and western blotting. Then, we constructed cell lines overexpressing ARNTL and knocked down ARNTL to explore its function and effect on chemotherapy sensitivity of NPC cell lines to cisplatin in vitro and vivo. Finally, we investigated the potential molecular mechanism of ARNTL by gene set enrichment analysis (GSEA), dual Luciferase reporter assay and chromatin immunoprecipitation assay.

Results
ARNTL was hypermethylated, and its mRNA and protein were significantly down-regulated in NPC cell lines and tissues. When treated by 5-aza-2′-deoxycytidine, mRNA expression was up-regulated. Overexpression of ARNTL could suppress NPC cells proliferation in vitro and vivo while silencing of ARNTL using shRNA achieved opposite results. GSEA assay found that ARNTL was associated with cell cycle and ectopic ARNTL overexpression could induce G2-M phase arrest. Then, we identified and validated cyclin-dependent kinase 5 (CDK5) as the targeting gene of ARNTL by dual Luciferase reporter assay and chromatin immunoprecipitation assay. When transiently infected ARNTL-overexpression cells with PENTER-vector or PENTER-CDK5 plasmids, the later could reverse the suppressive effects of ARNTL on NPC cell proliferation. Moreover, ARNTL significantly enhanced sensitivity to cisplatin in NPC cells.

Conclusions
ARNTL suppresses NPC cell proliferation and enhances sensitivity to cisplatin by targeting CDK5. ARNTL may represent a novel therapeutic target for NPC.