International journal of sports and exercise medicine, Oct 31, 2015
that participants stated that they "feel better", were "more motivated" and "uplifted" after the ... more that participants stated that they "feel better", were "more motivated" and "uplifted" after the program. The patient interviews also provided insights to the primary motivators (e.g., social support, improvements in strength and function, weight loss) and barriers (e.g., family and health issues) in adhering to the program and provided suggestions for improving the program (e.g., incorporating nutritional and treatment related side-effect discussions). Our results suggest that community-based lifestyle interventions may improve QoL and depression in AA BCa survivors and lend insights for improving future programs.
The proportion of patients diagnosed with colorectal cancer (CRC) at age < 50 (early-onset CRC... more The proportion of patients diagnosed with colorectal cancer (CRC) at age < 50 (early-onset CRC, or EOCRC) has steadily increased over the past three decades relative to the proportion of patients diagnosed at age ≥ 50 (late-onset CRC, or LOCRC), despite the reduction in CRC incidence overall. An important gap in the literature is whether EOCRC shares the same community-level risk factors as LOCRC. Thus, we sought to (1) identify disparities in the incidence rates of EOCRC and LOCRC using geospatial analysis and (2) compare the importance of community-level risk factors (racial/ethnic, health status, behavioral, clinical care, physical environmental, and socioeconomic status risk factors) in the prediction of EOCRC and LOCRC incidence rates using a random forest machine learning approach. The incidence data came from the Surveillance, Epidemiology, and End Results program (years 2000–2019). The geospatial analysis revealed large geographic variations in EOCRC and LOCRC incidence r...
Respiratory syncytial virus (RSV) infections and hospitalization have surged sharply among young ... more Respiratory syncytial virus (RSV) infections and hospitalization have surged sharply among young children. Here we test how the seasonal patterns of RSV infections in 2022 compared with those from other COVID-19 pandemic and pre-pandemic years. For this purpose, we analyzed a nation-wide and real-time database of electronic health records of 56 million patients across 50 states in the US. The monthly incidence rate of first-time RSV infection in young children (<5 years of age) and very young children (<1 year of age) followed a seasonal pattern from 2010 to 2019 with increases during the autumn, peaking in winter, subsiding in spring and summer. This seasonal pattern was significantly disrupted during the COVID-19 pandemic. In 2020, the incidence rate of RSV infections was remarkably low throughout the year. In 2021, the RSV season expanded to 9 months starting in the early summer and peaking in October. In 2022, RSV infections started to rise in May and were significantly hi...
The Youth Enjoy Science/Scientific Enrichment and Opportunity (YES/SEO) Program at Case Western R... more The Youth Enjoy Science/Scientific Enrichment and Opportunity (YES/SEO) Program at Case Western Reserve University (CWRU) School of Medicine and the Case Comprehensive Cancer Center (Case CCC) in Cleveland, OH is an intensive Research, Science, Technology, Engineering, and Mathematics (STEM) program targeted at engaging underrepresented minority high school students to better understand and to pursue careers in cancer research and healthcare. The program's long-range goals are to increase diversity of the cancer professional workforce to contribute to elimination of cancer health inequities. A challenging aspect of this intensive research and STEM education program is how to effectively teach about cancer health disparities and to address the importance of developing strategies for their remediation. We describe herein some innovative approaches utilized to engage students in learning about disparities and thinking about solutions. Overall, feedback from our students indicates the importance of introducing disparities education topics often and using multiple approaches, including small and large meetings as well as lecture and conversational formats. These approaches provide opportunities for frequent student engagement and concept reinforcement. Based on this experience, a series of recommendations are provided for incorporating disparities education into intensive research and STEM programs.
ImportanceThe association between cancer mortality and risk factors may vary by geography. Howeve... more ImportanceThe association between cancer mortality and risk factors may vary by geography. However, conventional methodological approaches rarely account for this variation.ObjectiveTo identify geographic variations in the association between risk factors and cancer mortality.Design, Setting, and ParticipantsThis geospatial cross-sectional study used county-level data from the National Center for Health Statistics for individuals who died of cancer from 2008 to 2019. Risk factor data were obtained from County Health Rankings & Roadmaps, Health Resources and Services Administration, and Centers for Disease Control and Prevention. Analyses were conducted from October 2021 to July 2022.Main Outcomes and MeasuresConventional random forest models were applied nationwide and by US region, and the geographical random forest model (accounting for local variation of association) was applied to assess associations between a wide range of risk factors and cancer mortality.ResultsThe study incl...
Women continue to be under-represented in science fields in Australia and internationally. Effort... more Women continue to be under-represented in science fields in Australia and internationally. Efforts to fix the 'leaky pipeline' producing this inequality are frustrated by declining enrolments in higher-level school science subjects. Researchers and policymakers need a better understanding of the factors which influence girls' decisions to take science in senior high school. In this pilot study, we examined whether growth mindset in science, achievement goal orientation, self-efficacy, and perceived peer and teacher support influenced intentions to study senior biology, chemistry, and physics. Participants were 125 adolescent girls aged between 14-17 years living in Australia. Online surveys were used to gather demographic and attitudinal data in a cross-sectional design. Regressions were used to examine the psychological and social factors that predicted subject-selection intentions. Self-efficacy in biology and social support from science teachers positively predicted intentions to study biology. Endorsing a growth mindset in science positively predicted intentions to study chemistry and physics. Selfefficacy for learning chemistry and physics positively predicted intentions to study those subjects. The results suggest that girls who have greater confidence in their ability in science and endorse a growth mindset are more likely to continue their study of physics and chemistry in the senior years of high school.
While a number of solid tumors are identified as obesity-associated cancers, multiple myeloma and... more While a number of solid tumors are identified as obesity-associated cancers, multiple myeloma and acute promyelocytic leukemia (APL) are the only hematologic malignancies included in this category. APL is a highly treatable form of AML characterized by maturation arrest at the promyelocyte stage, and frequent cures with combined ATRA and Arsenic Trioxide therapy. APL is initiated by a chromosomal translocation that causes the fusion of thePMLandRARAgenes, leading to the production of PML-RARA protein. To determine if obesity accelerates the development of APL, we used a genetically-engineered knock-in model in which human PML-RARA cDNA was inserted into the 5' untranslated region of the murine cathepsin G gene (Ctsg), which targets expression to early myeloid progenitor cells. This knock-in transgene was extensively backcrossed (>20 generations) into the C57BL/6J (B6) genetic background, which has been consistently shown to render mice susceptible to diet-induced obesity.Ctsg...
Recommendations v 6.2.1 Student engagement and development of geographic understanding of space, ... more Recommendations v 6.2.1 Student engagement and development of geographic understanding of space, place and interconnection 6.2.2 Localised curriculum and impacts on social resilience and community preparedness 6.2.4 Broadening horizons 7 Discussion and implications 8 Conclusion 9 Recommendations 10 References
Australia has seen declining numbers of students choosing mathematics and science subjects in the... more Australia has seen declining numbers of students choosing mathematics and science subjects in the senior secondary years, running counter to economic projections of an accelerating need for science and mathematics skills. Many students become less engaged with these subjects in the junior secondary years but attitudes such as selfconcept, utility value, and intrinsic value are important for subject selection decisions. We used latent profile analysis to examine the relationship between attitudes towards both subjects using data from 10,051 Australian Grade 8 students sampled by TIMSS 2015 and revealed six discrete groupings. While most students were at least attitudinally receptive to both subjects, there were many students who either resisted both or expressed a strong preference for one over another. Positive attitudes towards both subjects were mutually beneficial-better attitudes towards both were associated with higher achievement in each-but boys tended to be more positive towards both subjects and so benefitted from this relationship more than girls. Implications for educational research and teachers' practices are discussed.
Bone morphogenetic protein 4 (BMP4) signaling is activated in Barrett's esophagus, the condition ... more Bone morphogenetic protein 4 (BMP4) signaling is activated in Barrett's esophagus, the condition in which metaplastic columnar cells with malignant predisposition replace esophageal squamous cells damaged by GERD. In earlier studies, we reported that: 1) BMP4 activates expression of SOX9 (a transcription factor that can upregulate expression of columnar cytokeratins in esophageal squamous epithelium); and 2) BMP4 signaling can occur through BMP type I receptor-mediated activation of both the canonical pathway (through SMAD proteins) and the non-canonical pathway (through p38MAPK). Based on these findings, we hypothesized that an inhibitory SMAD would reduce canonical BMP4 signaling and SOX9 expression in Barrett's metaplasia. To explore this hypothesis, we sought to determine whether SMAD6, an inhibitory SMAD, decreases SOX9 expression in human Barrett's columnar cells and in esophageal squamous cells derived from patients with Barrett's esophagus. Methods: Telomerase-immortalized Barrett's (BAR-T and BAR-10T) and squamous (NES-B3T and NES-B10T) epithelial cell lines were transfected with inhibitory SMAD6 in the presence or absence of human recombinant BMP4. We performed: a) Western blot analysis for total and phosphorylated-SMAD1/5/8 (pSMAD1/5/8), total and phosphorylated-p38MAPK, NF-YB (a transcription factor downstream of the p38MAPK pathway), and SOX9; b) real-time PCR analysis for SOX9, ID1 (a BMP4 target gene activated by both canonical and non-canonical signaling), and MSX2 (a gene activated by SMADs); c) luciferase assay using an ID1 reporter construct; and d) chromatin immunoprecipitation (ChIP assay) for pSMAD1/5/8 or NF-YB binding to the SOX9 promoter. Results: In both squamous and Barrett's cell lines, SMAD6 transfection resulted in significant reductions in SOX9 and MSX2 expression and in transcriptional activity of ID1, all associated with decreased levels of pSMAD1/5/8. In contrast, SMAD6 transfection did not influence the p38MAPK pathway in any cell line. ChIP assay demonstrated that SMAD6 transfection decreased pSMAD1/5/8 binding to an identified SMAD binding element (SBE) on the SOX9 promoter. NF-YB binding to the CCATT box on the SOX9 promoter was not affected by transfection with SMAD6, further evidence that SMAD6 does not influence non-canonical BMP signaling. Conclusion: In both esophageal squamous and Barrett's columnar epithelial cells, SMAD6 reduces BMP4induced expression of SOX9 through effects on SMAD proteins, not on the p38MAPK pathway. These findings suggest that esophageal BMP4 signaling through the canonical SMAD pathway can induce squamous cells to express columnar cell transcription factors that might contribute to the pathogenesis of Barrett's esophagus. We speculate that agents targeting the SMAD pathway might prevent the development of Barrett's esophagus in patients with GERD.
Background: During hospitalization, older adults (+65) are inactive, which puts them at risk of f... more Background: During hospitalization, older adults (+65) are inactive, which puts them at risk of functional decline and loss of independence. Systematic strength training can prevent loss of functional performance. However, we lack knowledge about the effect of strength training commenced during hospitalization and continued after discharge in older medical patients. This assessor-blinded, randomized study investigated the effect of a simple, supervised strength training program for the lower extremities, combined with post-training protein supplementation during hospitalization and 4 weeks at home after discharge on change in mobility in older medical patients. Methods: Older medical patients (≥65 yrs) admitted acutely from their home to the Emergency Department were randomized to either standard care or supervised progressive strength training and an oral protein supplement during hospitalization and at home 3 days/week for 4 weeks after discharge. The primary outcome was between-g...
International journal of sports and exercise medicine, Oct 31, 2015
that participants stated that they "feel better", were "more motivated" and "uplifted" after the ... more that participants stated that they "feel better", were "more motivated" and "uplifted" after the program. The patient interviews also provided insights to the primary motivators (e.g., social support, improvements in strength and function, weight loss) and barriers (e.g., family and health issues) in adhering to the program and provided suggestions for improving the program (e.g., incorporating nutritional and treatment related side-effect discussions). Our results suggest that community-based lifestyle interventions may improve QoL and depression in AA BCa survivors and lend insights for improving future programs.
The proportion of patients diagnosed with colorectal cancer (CRC) at age < 50 (early-onset CRC... more The proportion of patients diagnosed with colorectal cancer (CRC) at age < 50 (early-onset CRC, or EOCRC) has steadily increased over the past three decades relative to the proportion of patients diagnosed at age ≥ 50 (late-onset CRC, or LOCRC), despite the reduction in CRC incidence overall. An important gap in the literature is whether EOCRC shares the same community-level risk factors as LOCRC. Thus, we sought to (1) identify disparities in the incidence rates of EOCRC and LOCRC using geospatial analysis and (2) compare the importance of community-level risk factors (racial/ethnic, health status, behavioral, clinical care, physical environmental, and socioeconomic status risk factors) in the prediction of EOCRC and LOCRC incidence rates using a random forest machine learning approach. The incidence data came from the Surveillance, Epidemiology, and End Results program (years 2000–2019). The geospatial analysis revealed large geographic variations in EOCRC and LOCRC incidence r...
Respiratory syncytial virus (RSV) infections and hospitalization have surged sharply among young ... more Respiratory syncytial virus (RSV) infections and hospitalization have surged sharply among young children. Here we test how the seasonal patterns of RSV infections in 2022 compared with those from other COVID-19 pandemic and pre-pandemic years. For this purpose, we analyzed a nation-wide and real-time database of electronic health records of 56 million patients across 50 states in the US. The monthly incidence rate of first-time RSV infection in young children (<5 years of age) and very young children (<1 year of age) followed a seasonal pattern from 2010 to 2019 with increases during the autumn, peaking in winter, subsiding in spring and summer. This seasonal pattern was significantly disrupted during the COVID-19 pandemic. In 2020, the incidence rate of RSV infections was remarkably low throughout the year. In 2021, the RSV season expanded to 9 months starting in the early summer and peaking in October. In 2022, RSV infections started to rise in May and were significantly hi...
The Youth Enjoy Science/Scientific Enrichment and Opportunity (YES/SEO) Program at Case Western R... more The Youth Enjoy Science/Scientific Enrichment and Opportunity (YES/SEO) Program at Case Western Reserve University (CWRU) School of Medicine and the Case Comprehensive Cancer Center (Case CCC) in Cleveland, OH is an intensive Research, Science, Technology, Engineering, and Mathematics (STEM) program targeted at engaging underrepresented minority high school students to better understand and to pursue careers in cancer research and healthcare. The program's long-range goals are to increase diversity of the cancer professional workforce to contribute to elimination of cancer health inequities. A challenging aspect of this intensive research and STEM education program is how to effectively teach about cancer health disparities and to address the importance of developing strategies for their remediation. We describe herein some innovative approaches utilized to engage students in learning about disparities and thinking about solutions. Overall, feedback from our students indicates the importance of introducing disparities education topics often and using multiple approaches, including small and large meetings as well as lecture and conversational formats. These approaches provide opportunities for frequent student engagement and concept reinforcement. Based on this experience, a series of recommendations are provided for incorporating disparities education into intensive research and STEM programs.
ImportanceThe association between cancer mortality and risk factors may vary by geography. Howeve... more ImportanceThe association between cancer mortality and risk factors may vary by geography. However, conventional methodological approaches rarely account for this variation.ObjectiveTo identify geographic variations in the association between risk factors and cancer mortality.Design, Setting, and ParticipantsThis geospatial cross-sectional study used county-level data from the National Center for Health Statistics for individuals who died of cancer from 2008 to 2019. Risk factor data were obtained from County Health Rankings & Roadmaps, Health Resources and Services Administration, and Centers for Disease Control and Prevention. Analyses were conducted from October 2021 to July 2022.Main Outcomes and MeasuresConventional random forest models were applied nationwide and by US region, and the geographical random forest model (accounting for local variation of association) was applied to assess associations between a wide range of risk factors and cancer mortality.ResultsThe study incl...
Women continue to be under-represented in science fields in Australia and internationally. Effort... more Women continue to be under-represented in science fields in Australia and internationally. Efforts to fix the 'leaky pipeline' producing this inequality are frustrated by declining enrolments in higher-level school science subjects. Researchers and policymakers need a better understanding of the factors which influence girls' decisions to take science in senior high school. In this pilot study, we examined whether growth mindset in science, achievement goal orientation, self-efficacy, and perceived peer and teacher support influenced intentions to study senior biology, chemistry, and physics. Participants were 125 adolescent girls aged between 14-17 years living in Australia. Online surveys were used to gather demographic and attitudinal data in a cross-sectional design. Regressions were used to examine the psychological and social factors that predicted subject-selection intentions. Self-efficacy in biology and social support from science teachers positively predicted intentions to study biology. Endorsing a growth mindset in science positively predicted intentions to study chemistry and physics. Selfefficacy for learning chemistry and physics positively predicted intentions to study those subjects. The results suggest that girls who have greater confidence in their ability in science and endorse a growth mindset are more likely to continue their study of physics and chemistry in the senior years of high school.
While a number of solid tumors are identified as obesity-associated cancers, multiple myeloma and... more While a number of solid tumors are identified as obesity-associated cancers, multiple myeloma and acute promyelocytic leukemia (APL) are the only hematologic malignancies included in this category. APL is a highly treatable form of AML characterized by maturation arrest at the promyelocyte stage, and frequent cures with combined ATRA and Arsenic Trioxide therapy. APL is initiated by a chromosomal translocation that causes the fusion of thePMLandRARAgenes, leading to the production of PML-RARA protein. To determine if obesity accelerates the development of APL, we used a genetically-engineered knock-in model in which human PML-RARA cDNA was inserted into the 5' untranslated region of the murine cathepsin G gene (Ctsg), which targets expression to early myeloid progenitor cells. This knock-in transgene was extensively backcrossed (>20 generations) into the C57BL/6J (B6) genetic background, which has been consistently shown to render mice susceptible to diet-induced obesity.Ctsg...
Recommendations v 6.2.1 Student engagement and development of geographic understanding of space, ... more Recommendations v 6.2.1 Student engagement and development of geographic understanding of space, place and interconnection 6.2.2 Localised curriculum and impacts on social resilience and community preparedness 6.2.4 Broadening horizons 7 Discussion and implications 8 Conclusion 9 Recommendations 10 References
Australia has seen declining numbers of students choosing mathematics and science subjects in the... more Australia has seen declining numbers of students choosing mathematics and science subjects in the senior secondary years, running counter to economic projections of an accelerating need for science and mathematics skills. Many students become less engaged with these subjects in the junior secondary years but attitudes such as selfconcept, utility value, and intrinsic value are important for subject selection decisions. We used latent profile analysis to examine the relationship between attitudes towards both subjects using data from 10,051 Australian Grade 8 students sampled by TIMSS 2015 and revealed six discrete groupings. While most students were at least attitudinally receptive to both subjects, there were many students who either resisted both or expressed a strong preference for one over another. Positive attitudes towards both subjects were mutually beneficial-better attitudes towards both were associated with higher achievement in each-but boys tended to be more positive towards both subjects and so benefitted from this relationship more than girls. Implications for educational research and teachers' practices are discussed.
Bone morphogenetic protein 4 (BMP4) signaling is activated in Barrett's esophagus, the condition ... more Bone morphogenetic protein 4 (BMP4) signaling is activated in Barrett's esophagus, the condition in which metaplastic columnar cells with malignant predisposition replace esophageal squamous cells damaged by GERD. In earlier studies, we reported that: 1) BMP4 activates expression of SOX9 (a transcription factor that can upregulate expression of columnar cytokeratins in esophageal squamous epithelium); and 2) BMP4 signaling can occur through BMP type I receptor-mediated activation of both the canonical pathway (through SMAD proteins) and the non-canonical pathway (through p38MAPK). Based on these findings, we hypothesized that an inhibitory SMAD would reduce canonical BMP4 signaling and SOX9 expression in Barrett's metaplasia. To explore this hypothesis, we sought to determine whether SMAD6, an inhibitory SMAD, decreases SOX9 expression in human Barrett's columnar cells and in esophageal squamous cells derived from patients with Barrett's esophagus. Methods: Telomerase-immortalized Barrett's (BAR-T and BAR-10T) and squamous (NES-B3T and NES-B10T) epithelial cell lines were transfected with inhibitory SMAD6 in the presence or absence of human recombinant BMP4. We performed: a) Western blot analysis for total and phosphorylated-SMAD1/5/8 (pSMAD1/5/8), total and phosphorylated-p38MAPK, NF-YB (a transcription factor downstream of the p38MAPK pathway), and SOX9; b) real-time PCR analysis for SOX9, ID1 (a BMP4 target gene activated by both canonical and non-canonical signaling), and MSX2 (a gene activated by SMADs); c) luciferase assay using an ID1 reporter construct; and d) chromatin immunoprecipitation (ChIP assay) for pSMAD1/5/8 or NF-YB binding to the SOX9 promoter. Results: In both squamous and Barrett's cell lines, SMAD6 transfection resulted in significant reductions in SOX9 and MSX2 expression and in transcriptional activity of ID1, all associated with decreased levels of pSMAD1/5/8. In contrast, SMAD6 transfection did not influence the p38MAPK pathway in any cell line. ChIP assay demonstrated that SMAD6 transfection decreased pSMAD1/5/8 binding to an identified SMAD binding element (SBE) on the SOX9 promoter. NF-YB binding to the CCATT box on the SOX9 promoter was not affected by transfection with SMAD6, further evidence that SMAD6 does not influence non-canonical BMP signaling. Conclusion: In both esophageal squamous and Barrett's columnar epithelial cells, SMAD6 reduces BMP4induced expression of SOX9 through effects on SMAD proteins, not on the p38MAPK pathway. These findings suggest that esophageal BMP4 signaling through the canonical SMAD pathway can induce squamous cells to express columnar cell transcription factors that might contribute to the pathogenesis of Barrett's esophagus. We speculate that agents targeting the SMAD pathway might prevent the development of Barrett's esophagus in patients with GERD.
Background: During hospitalization, older adults (+65) are inactive, which puts them at risk of f... more Background: During hospitalization, older adults (+65) are inactive, which puts them at risk of functional decline and loss of independence. Systematic strength training can prevent loss of functional performance. However, we lack knowledge about the effect of strength training commenced during hospitalization and continued after discharge in older medical patients. This assessor-blinded, randomized study investigated the effect of a simple, supervised strength training program for the lower extremities, combined with post-training protein supplementation during hospitalization and 4 weeks at home after discharge on change in mobility in older medical patients. Methods: Older medical patients (≥65 yrs) admitted acutely from their home to the Emergency Department were randomized to either standard care or supervised progressive strength training and an oral protein supplement during hospitalization and at home 3 days/week for 4 weeks after discharge. The primary outcome was between-g...
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