bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carfilzomib monotherapy in Japanese patients with relapsed or refractory multiple myeloma: A phase 1/2 study
Authors: Iida Shinsuke , Watanabe Takashi , Matsumoto Morio , Suzuki Kenshi , Sunami Kazutaka , Ishida Tadao , Ando Kiyoshi , Chou Takaaki , Ozaki Shuji , Taniwaki Masafumi , Uike Naokuni , Shibayama Hirohiko , Hatake Kiyohiko , Izutsu Koji , Ishikawa Takayuki , Shumiya Yoshihisa , Tobinai Kensei 
Published: July 2019

AbstractThis multicenter, open‐label phase 1/2 study evaluated single‐agent carfilzomib in 50 heavily pretreated Japanese patients with relapsed/refractory multiple myeloma (median of five prior treatments). In phase 1, patients were dosed at three levels: 15, 20, or 20/27 mg/m2. Maximum tolerated dosage was not reached at the tolerability evaluation. Patients in phase 2 were treated with 20/27 mg/m2 carfilzomib. Median duration of exposure to carfilzomib in the 20/27 mg/m2 group at this final analysis was 4.7 months (range: 0.3‐39.4). Overall response rate in the 20/27 mg/m2 group, primary endpoint of the study, was 22.5% (n = 9) (95% confidence interval, 12.3‐37.5) with 2.5% (n = 1) stringent complete response. Median progression‐free survival and overall survival in the 20/27 mg/m2 group were 5.1 months (95% CI, 2.8‐13.6) and 22.9 months (95% CI, 14.1‐not estimable), respectively. Frequently occurring grade ≥3 adverse events in the 20/27 mg/m2 group included lymphopenia (72.5%), neutropenia (40.0%), and leukopenia (32.5%). Giving long‐term carfilzomib monotherapy led to long‐term overall survival for heavily pretreated multiple myeloma patients with a favorable safety profile. Carfilzomib monotherapy can be a good option for heavily pretreated multiple myeloma patients.
SALL4 promotes the tumorigenicity of cervical cancer cells through activation of the Wnt/β‐catenin pathway via CTNNB1
Authors: Chen Mei , Li Lu , Zheng Peng‐Sheng 
Published: July 2019

AbstractSALL4 is overexpressed in many cancers and is found to be involved in tumorigenesis and tumor progression. However, the function of SALL4 in cervical cancer remains unknown. Here, we showed that the expression of SALL4 was gradually increased from normal cervical tissue to high‐grade squamous intraepithelial lesions and then to squamous cervical carcinoma. SALL4 was upregulated or downregulated in cervical cancer cells by stably transfecting a SALL4‐expressing plasmid or a shRNA plasmid targeting SALL4, respectively. In vitro, cell growth curves and MTT (3‐(4,5‐dimethylthiazole‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assays showed that SALL4 promoted the cell proliferation of cervical cancer cells. In vivo, xenograft experiments verified that SALL4 enhanced the tumor formation of cervical cancer cells in female BALB/c Nude mice. Cell cycle analysis by fluorescence‐activated cell sorting found that SALL4 accelerates cell cycle transition from the G0/G1 phase to the S phase. TOP/FOP‐Flash reporter assay revealed that SALL4 significantly upregulates the activity of Wnt/β‐catenin pathway. Western blotting showed that the expression levels of β‐catenin and important downstream genes, including c‐Myc and cyclin D1, were increased by SALL4 in cervical cancer cells. Furthermore, dual‐luciferase reporter and chromatin immunoprecipitation assays confirmed that SALL4 transcriptionally activated CTNNB1 by physically interacting with its promoters. Taken together, The results of this study demonstrated that SALL4 may promote cell proliferation and tumor formation of cervical cancer cells by upregulating the activity of the Wnt/β‐catenin signaling pathway by directly binding to the CTNNB1 promoter and trans‐activating CTNNB1.
What do children think about their social worker? A Q‐method study of children's services
Authors: Stabler Lorna , Wilkins David , Carro Hester 
Published: July 2019

AbstractUnderstanding how children experience social work interventions is an important part of gauging whether what is provided is genuinely helpful. In this paper, we describe the findings from a research project using Q‐method, aimed at understanding what children involved with statutory services think about their social workers and how they experience the time they spend together. Using a pre‐existing practice framework, we explored skills including empathy, collaboration, and purposefulness from the point of view of children and young people. The participants in our study (n = 22) were insightful observers of social work practice, able to describe not only how they experienced time spent with their workers but also inferring differences in motivation and approach. In addition, workers who were described in similar terms by different young people were nevertheless experienced differently. This suggests not an archetypal “good social worker”—instead, there are skills that are good for specific children at specific times within the context of specific relationships.
dl‐3‐n‐butylphthalide preserves white matter integrity and alleviates cognitive impairment in mice with chronic cerebral hypoperfusion
Authors: Han Qin‐Yu , Zhang He , Zhang Xi , He Dong‐Sheng , Wang Sun‐Wei , Cao Xiang , Dai Yu‐Tian , Xu Yun , Han Li‐Juan 
Published: July 2019

AbstractAimsEffects of dl‐3‐n‐butylphthalide (NBP) on white matter damage and cognitive impairment in vascular cognitive impairment (VCI) have not been well studied. This study aimed to investigate the effects of NBP treatment on chronic cerebral hypoperfusion‐induced white matter lesions and cognitive dysfunction in mice.MethodsMice were subjected to bilateral common carotid artery stenosis (BCAS) for over 30 days. The cerebral blood flow was detected using a laser Doppler flowmetry. Cognitive functions were assessed by several behavioral tests. We also evaluated the effects of NBP on the blood‐brain barrier (BBB) disruption and reactive astrogliosis, using Evans Blue extravasation, Western blot, CBA, and immunofluorescence in BCAS mice and cultured astrocytes.ResultsThe results indicated that NBP treatment attenuated spatial memory dysfunction while promoted cerebral perfusion and white matter integrity in BCAS mice. Moreover, NBP treatment prevented BBB leakage and damage of endothelial cells, as well as disruption of endothelial tight junctions. Furthermore, NBP administration effectively decreased the number of activated astrocytes and pro‐inflammatory cytokines, as well as the production of MMPs, in BCAS‐induced mice and LPS‐stimulated astrocytes.ConclusionOur results indicated that NBP represents a promising therapy for chronic cerebral hypoperfusion‐induced white matter damage and cognitive impairment.
Urinary dysfunction in patients with rectal cancer: a prospective cohort study
Authors: Karlsson L. , Bock D. , Asplund D. , Ohlsson B. , Rosenberg J. , Angenete E. 
Published: July 2019

AbstractAimUrinary dysfunction is one of many complications after treatment for rectal cancer. The aim of this study was to evaluate the prevalence of patient‐reported urinary dysfunction at the time of diagnosis and at 1‐year follow‐up and to assess the risk factors linked to urinary incontinence.MethodPatients with newly diagnosed rectal cancer were included in the QoLiRECT study between 2012 and 2015. Questionnaires from the time of diagnosis and 1‐year follow‐up were analysed, with 1085 and 916 patients, respectively, eligible for analysis. Regression analyses were made to investigate possible risk factors for incontinence. The patient cohort was also compared with a cohort from the Swedish general population.ResultsAt baseline, the prevalence of urinary dysfunction (14% of women, 8% of men) was similar to that in the general population. At 1‐year follow‐up, 20% of patients experienced urinary incontinence (29% of women, 14% of men). Emptying difficulties were experienced by 46% (41% of women, 49% of men) and urgency by 58% across both sexes. Abdominoperineal excision and urinary dysfunction at baseline were found to be independent risk factors for incontinence at 1‐year follow‐up. Among patients who were continent at baseline, risk factors were female sex, physical inactivity at baseline, comorbidity and abdominoperineal excision.ConclusionUrinary dysfunction is frequent among patients with rectal cancer, with up to a two‐fold increase in symptoms 1 year after diagnosis. Unfortunately, few factors are modifiable and these results stress the importance of informing patients of possible outcomes related to urinary dysfunction after treatment for rectal cancer.
Cognitive assessment in a predominantly Hispanic and Native American population in New Mexico and its association with kidney transplant wait‐listing
Authors: Ng Yue‐Harn , Al Mawed Saleem , Pankratz Vernon Shane , Argyropoulos Christos , Singh Pooja , Shaffi Saeed Kamran , Myaskovsky Larissa , Unruh Mark , Harford Antonia 
Published: July 2019

AbstractThe association between cognitive function and the likelihood of kidney transplant (KT) wait‐listing, especially in minority populations, has not been clearly delineated. We performed a retrospective review of our pre‐KT patients, who consist mainly of Hispanics and Native Americans, over a 16‐month period. We collected data on baseline demographics and the Montreal Cognitive Assessment (MoCA) score, at the initial KT evaluation. We defined cognitive impairment as MoCA scores of <24. We constructed linear regression models to identify associations between baseline characteristics with MoCA scores and used Cox proportional hazards models to assess associations between MoCA score and KT wait‐listing. During the study period, 154 patients completed the MoCA during their initial evaluation. Mean (standard deviation) MoCA scores were 23.9 (4.6), with 58 (38%) participants scoring <24. Advanced age, lower education and being on dialysis were associated with lower MoCA scores. For every one‐point increase in MoCA, the likelihood of being wait‐listed increased 1.10‐fold (95% CI 1.01‐1.19, P = .022). Being Native American and having kidney disease due to diabetes or hypertension were associated with longer time to wait‐listing. Cognitive impairment was common in our pre‐KT patients and was associated with a lower likelihood of KT wait‐listing.
Optimistically biased perception of one's own skin cancer risk: Representative nationwide findings
Authors: Diehl Katharina , Görig Tatiana , Osenbrügge Nina , Schilling Laura , Greinert Rüdiger , Schneider Sven 
Published: July 2019

SummaryBackgroundPrevious research has shown that individuals tend to have unrealistic comparative optimism (UCO) for different diseases and health outcomes. Our aim was to analyze UCO in relation to skin cancer for the first time in a representative nationwide sample. The results will be important for planning future prevention.MethodsThe National Cancer Aid Monitoring on Sunbed Use (NCAM, wave 3) is a representative nationwide German survey (n = 3,000, 14–45 years). We assessed UCO in relation to skin cancer and analyzed its association with sociodemographics, tanning and health‐related risk behaviors, skin cancer risk, and skin cancer risk awareness.ResultsFour out of ten (43.3 %) respondents believed themselves to have a lower risk of developing skin cancer than other people of the same age and sex. Younger individuals were more likely to be optimistic. Individuals with an increased risk of skin cancer were more likely to perceive this higher risk.ConclusionWhile it is realistic for those who actually have a higher risk of skin cancer to perceive it that way, the findings for the general population (and specifically for younger individuals) are concerning. It seems important to explain to people that their perception of their own risk of skin cancer is unrealistic, as this may affect their individual screening and prevention behavior.
Development of dopaminergic genetic associations with visuospatial, verbal and social working memory
Authors: Dumontheil Iroise , Kilford Emma J. , Blakemore Sarah‐Jayne 
Published: July 2019

AbstractDopamine transmission in the prefrontal cortex (PFC) supports working memory (WM), the temporary holding, processing and manipulation of information in one's mind. The gene coding the catechol‐O‐methyltransferase (COMT) enzyme, which degrades dopamine, in particular in the PFC, has a common single nucleotide polymorphism leading to two versions of the COMT enzyme which vary in their enzymatic activity. The methionine (Met) allele has been associated with higher WM performance and lower activation of the PFC in executive function tasks than the valine (Val) allele. In a previous study, COMT genotype was associated with performance on verbal and visuospatial WM tasks in adults, as well as with performance on a novel social WM paradigm that requires participants to maintain and manipulate information about the traits of their friends or family over a delay. Here, data collected in children and adolescents (N = 202) were compared to data from the adult sample (N = 131) to investigate possible age differences in genetic associations. Our results replicate and extend previous work showing that the pattern of superior WM performance observed in Met/Met adults emerges during development. These findings are consistent with a decrease in prefrontal dopamine levels during adolescence. Developmentally moderated genetic effects were observed for both visuospatial and social WM, even when controlling for non‐social WM performance, suggesting that the maintenance and manipulation of social information may also recruit the dopamine neurotransmitter system. These findings show that development should be considered when trying to understand the impact of genetic polymorphisms on cognitive function.
Evaluation of lipoprotein‐associated phospholipase A2 as a marker for renal microvasculopathy in adolescents with Type 1 diabetes
Authors: Seyfarth J. , Herebian D. , Reinauer C. , Baechle C. , Roden M. , Holl R. W. , Reinehr T. , Mayatepek E. , Meissner T. , Rosenbauer J. 
Published: July 2019

AbstractAimTo assess the relevance of lipoprotein‐associated phospholipase A2 activity as a diagnostic and prognostic marker for renal microvascular diseases.MethodsWe analysed lipoprotein‐associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes‐Patients Follow‐up (DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow‐up. Relationships between lipoprotein‐associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression.ResultsLipoprotein‐associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow‐up. Lipoprotein‐associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein‐associated phospholipase A2 activity. Cross‐sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein‐associated phospholipase A2 activity with HbA1c and HDL‐cholesterol.ConclusionsLipoprotein‐associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein‐associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro‐ and macrovascular diseases in Type 1 diabetes.
Commentary: SGLT inhibitors in type 1 diabetes: Place in therapy and a risk mitigation strategy for preventing diabetic ketoacidosis ‐ the STOP DKA protocol
Authors: Rendell Marc S. 
Published: July 2019

AbstractIn the accompanying article, Goldenberg et al. review the promotion of diabetic ketoacidosis by SGLT2 inihibitors. They have carried out a metanalysis showing a 3.5‐fold increase in the risk of diabetic ketoacidosis (DKA) in patients with type 1 diabetes under treatment with SGLT2 inhibitors. They make a number of suggestions for attempting to mitigate the risk of DKA in these patients, notably including blood ketone monitoring and the use of supplemental carbohydrates with additional insulin when ketones suggest incipient DKA. Their proposal merits evaluation in a clinical trial involving type 1 diabetes, which should also assess the possible cardiorenal benefits demonstrated with treatment with SGLT2 inhibitors in type 2 diabetes.
Using Real‐Life Major League Baseball Data in an Introductory Statistics Course
Authors: Wathen Samuel , Rhew Nicholas D. 
Published: July 2019

ABSTRACTA primary goal of introductory statistics courses is to develop a student's ability to think statistically. To motivate students to this end, the literature suggests that statistics courses use exercises that are relevant and familiar to students. Work in educational psychology highlights the importance of connecting new concepts to pre‐existing knowledge, mental models, or schema. One method to meet these criteria is to develop exercises and problems that use real‐life data. While real‐life data provide a context for the application of statistical methods, the data does not necessarily provide a context or process for developing the ability to think statistically. This teaching brief describes a set of logical, sequential, and ready‐to‐use exercises that motivate statistical inquiry and thought in line with the GAISE College Report recommendations. The exercises use real‐life data freely sourced from Major League Baseball and the nonfiction story ofMoneyball: The Art of Winning an Unfair Game. Student reactions indicate that these exercises, which are anchored in real‐life data with a real‐life story, are successful in motivating student interest in statistics.
Identifying Cognitive Processing Events during Clicker Exercises and Exploring Their Relationship with Student Learning
Authors: D'Souza Derrick E. , Daspit Joshua J. , Sigdyal Pratigya 
Published: July 2019

ABSTRACTThe use of clickers in the classroom has been linked to student learning. However, studies that examine the effects of clickers on learning often conceptualize a clicker exercise as a single, homogeneous cognitive processing (CP) event. We offer a conceptualization of sequenced cognitive activities that unfold during a clicker exercise. An inductive approach is adopted to identify three CP events that occur during a clicker exercise: an investigation event, a confirmation event, and a ratification event. We then use data collected from a sample of 187 students in an undergraduate business capstone course to explore the relationships between the three CP events and student learning. Contrary to expectations, not all CP events contribute positively to student learning. We discuss the implications of these findings and offer directions for future research that advance the understanding of clicker‐enhanced student learning. These insights afford instructors new options for optimizing the contributions of clicker exercises to student learning in their courses.
In vitro evidence consistent with an interaction between wild‐type and mutant SOD1 protein associated with canine degenerative myelopathy
Authors: Qi Yao , Montague Paul , Loney Colin , Campbell Clare , Shafie Intan N. F. , Anderson Thomas J. , McLaughlin Mark 
Published: July 2019

AbstractCanine degenerative myelopathy (DM) is a progressive neurological disorder that may be considered to be a large animal model for specific forms of the fatal human disease, familial amyotrophic lateral sclerosis (fALS). DM is associated with a c118G>A mutation of the superoxide dismutase 1 (Sod1) gene, and a significant proportion of cases are inherited in an autosomal recessive manner in contrast to the largely, but not exclusively, dominant mode of inheritance in fALS. The consensus view is that these Sod1/SOD1 mutations result in a toxic gain of function but the mechanisms remain unclear. Here we used an in vitro neuroblastoma cell line transfection system to monitor wild‐type and mutant forms of SOD1 fusion proteins containing either a Cherry or an enhanced green fluorescent protein (EGFP) tag. These fusion proteins retained SOD1 enzymatic activity on a native gel assay system. We demonstrate that SOD1 aggregate density is significantly higher in DM transfectants compared to wild‐type. In addition, we show by co‐immunoprecipitation and confocal microscopy, evidence for a potential interaction between wild‐type and mutant forms of SOD1 in co‐transfected cells. While in vitro studies have shown SOD1 heterodimer formation in fALS models, this is the first report for DM SOD1. Therefore, despite for the majority of cases there is a difference in the mode of inheritance between fALS and DM, a similar interaction between wild‐type and mutant SOD1 forms can occur. Clarifying the role of SOD1 in DM may also be of benefit to understanding the role of SOD1 in fALS.
Influence of age at seizure onset on the acquisition of neurodevelopmental skills in an SCN8A cohort
Authors: Encinas Alejandra C. , Moore Ida (Ki) M. , Watkins Joseph C. , Hammer Michael F. 
Published: July 2019

AbstractObjectiveTo characterize a cohort of patients with SCN8A‐related epilepsy and to perform analyses to identify correlations involving the acquisition of neurodevelopmental skills.MethodsWe analyzed patient data (n = 91) submitted to an online registry tailored to characteristics of children with SCN8A variants. Participants provided information on the history of their child's seizures, medications, comorbidities, and developmental skills based on the Denver II items. Spearman rank tests were utilized to test for correlations among a variety of aspects of seizures, medications, and neurodevelopmental progression.ResultsThe 91 participants carried 71 missense variants (41 newly reported) and three truncating variants. Ages at seizure onset ranged from birth to >12 months of age (mean ± SD = 5 months 21 days ± 7 months 14 days). Multiple seizure types with multimodal onset times and developmental delay were observed as general features of this cohort. We found a positive correlation between a developmental score based upon percentage of acquired skills and the age at seizure onset, current seizure freedom, and initial febrile seizures. Analyses of cohort subgroups revealed clear distinctions between patients who had a single reported variant in SCN8A and those with an additional variant reported in a gene other than SCN8A, as well as between patients with different patterns of regression before and at seizure onset.SignificanceThis is the first study of an SCN8A patient cohort of this size and for which correlations between age at seizure onset and neurodevelopment were investigated. Our correlation studies suggest that variants of uncertain significance should be considered in assessing children with SCN8A‐related disorders. This study substantially improves the characterization of this patient population and our understanding of the neurodevelopmental effects associated with seizures for SCN8A patients, and provides a clinical context at initial presentation that may be prognostic for developmental outcome.