tbuckley/cabot-search huggingface dataset:
Addressing Health Equity in Public Health Practice: Frameworks, Promising Strategies, and Measurement Considerations
Authors: Leandris C. Liburd, Jeffrey E. Hall, Jonetta J. Mpofu, Sheree Marshall Williams, Karen Bouye, Ana Penman-Aguilar
Journal: Annual Review of Public Health (2020)

This review describes the context of health equity and options for integrating equity into public health practice. We first discuss how the conceptualization of health equity and how equity considerations in US public health practice have been shaped by multidisciplinary engagements. We then discuss specific ways to address equity in core public health functions, provide examples of relevant frameworks and promising strategies, and discuss conceptual and measurement issues relevant to assessing progress in moving toward health equity. Challenges and opportunities and their implications for future directions are identified.
Outcome of Men With Relapses After Adjuvant Bleomycin, Etoposide, and Cisplatin for Clinical Stage I Nonseminoma
Authors: Stefanie Fischer, Torgrim Tandstad, Gabriella Cohn-Cedermark, Constance Thibault, Bruno Vincenzi, Dirk Klingbiel, Costantine Albany, Andrea Necchi, Angelika Terbuch, Anja Lorch, Jorge Aparicio, Axel Heidenreich, Marcus Hentrich, Matthew Wheater, Carl W. Langberg, Olof Ståhl, Christian Daniel Fankhauser, Anis A. Hamid, Konstantinos Koutsoukos, Jonathan Shamash, Jeff White, Carsten Bokemeyer, Jörg Beyer, Silke Gillessen
Journal: Journal of Clinical Oncology (2019)

Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment.Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses.Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; P = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes.Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).
Clinical features and outcome of sporadic colorectal carcinoma in young adults: A single center, cross sectional analysis.
Authors: Muhammad Nauman Zahir, Eisha Mahpara, Sobia Rafiq, Kulsoom Ghias, Munira Shabbir-Moosajee
Journal: Journal of Clinical Oncology (2013)

e14680 Background: Early onset colorectal carcinoma (CRC), defined as CRC at age below 45 years is rare. However, an increasing incidence has been noted in Southeast Asia. It is hypothesized to be a biologically and clinically distinct entity personifying aggressive disease and a worse survival. Data on this subject is scarce from this part of the world and hence our objective was to study the clinical presentation and outcome of early onset sporadic CRC in patients at a single tertiary care center in Pakistan. Methods: Data was collected by a retrospective chart review. 131 patients were found eligible for the period between January 1, 2004 and December 31, 2011. A pre-designed and coded questionnaire was used and analysis was done using SPSS. Cox proportional hazard model was used to compute prevalence ratios. Results: Early onset sporadic CRC accounted for 32% of all CRC treated in the specified time period. Colon and rectal cancers accounted for 55% and 45% of patients respectively. The median age was 35 years (range 16-45 years) and the male to female ratio was 2:1. 74% of patients presented with advanced stage disease [stages III (45%) and IV (29%)]. On comparison, bleeding per rectum, signet ring morphology, stage and grade of tumor were found to be statistically significant for the rectal cancer group on a univariate analysis. 93% of rectal carcinoma patients received appropriate surgery and/or neoadjuvant/adjuvant therapy as opposed to 69% of colon cancers. Median survival was 19 months (range 0-112.5 months). However, Kaplan-Meier analysis revealed a trend towards an inferior survival for rectal carcinoma 2 years after initial diagnosis (p=0.56). Conclusions: Higher incidence of early onset CRC is noted in our population as compared to the western literature. Rectal carcinoma accounts for almost half the patients in this young CRC population. This group was found to have a higher frequency of poor prognostic factors. However, we have noted a similar 2 year survival between the 2 groups, with a trend towards an inferior prognosis with longer followup. It is possible that a larger sample size may have elucidated a statistically significant difference between the two groups.
Effect of ROR1-targeting small molecules on chronic lymphocytic leukemia (CLL) cells.
Authors: Hakan Mellstedt, Salam Khan, Jan Vågberg, Styrbjörn Byström, Johan Schultz, Mohammad Hojat Farsangi, Ladan Mansouri, Amir Hossein Danesh Manesh, Anders Österborg, Ali Moshfegh
Journal: Journal of Clinical Oncology (2012)

6557 Background: There is a great interest to develop targeting drugs for CLL, both MAbs and small molecules, to improve the outcome for the disease. ROR1, a receptor tyrosine kinase, is overexpressed on CLL cells but not on normal cells. ROR1 is constitutively phosphorylated and siRNA transfection induces leukemic cell death. The aim of the study is to produce small molecules inhibiting the cytoplasmic tyrosine kinase activity of ROR1, which could induce specific killing of leukemic cells. Methods: A high-throughput screening assay in 384-format has been developed measuring phosphorylation of a substrate peptide by human recombinant intracellular ROR-1 kinase domain. A collection of 80.000 small molecules has been screened generating two chemical series. Novel leads have been synthesized and structure-activity-relationship has been developed using the assay. Results: Three compounds were selected (KAN0173631, KAN0438063, KAN0438175T). Freshly isolated leukemic CLL cells were used as targets in addition to PBMC from healthy donors to test cytotoxicity. The three compounds induced specific apoptosis of CLL cells (Annexin V/PI and MTT) both at 24 and 48h. Efficacy index (EI), i.e. killing of leukemic cells in relation to normal PBMC was favourable. The most promising drug KAN0438063 had an EI of 40 i.e. killed 40 times more CLL cells than PBMC at an IC 50 of 10µM. The compounds induced PARP cleavage and cleavage of caspases 8 and 9 as well as down regulation of Mcl-1 and Bcl-xl (Western Blot). ROR1 was dephosphorylated (Western Blot). The selective apoptotic effect was compared to other small molecules targeting non-ROR1 structures in CLL (PCI-32765, CAL-101, R406, R788, STK-156485, STK-156133) and our compounds were significantly more effective (EI) (p&lt;0.001). Conclusions: We have developed effective and selective series of compounds targeting ROR1 with promising ADMET properties. ROR1 targeting small molecules might also be effective for other tumor cells expressing ROR1 as has been noted for e.g. pancreatic carcinoma cells. Our model molecules will be further optimized and tested in animal tumor models. These molecules represent the first small molecules targeting ROR1 – a “survival factor” in CLL.
Long-Term Exposure to Ambient Fine Particulate Matter (PM2.5) and Lung Function in Children, Adolescents, and Young Adults: A Longitudinal Cohort Study
Authors: Cui Guo, Gerard Hoek, Ly-yun Chang, Yacong Bo, Changqing Lin, Bo Huang, Ta-chien Chan, Tony Tam, Alexis K. H. Lau, Xiang Qian Lao
Journal: Environmental Health Perspectives (2019)

The association between long-term exposure to ambient fine particulate matter with aerodynamic diameter ≤2.5μm (PM2.5) and lung function in young people remains uncertain, particularly in Asia, where air pollution is generally a serious problem.This study investigated the association between long-term exposure to ambient PM2.5 and lung function in Taiwanese children, adolescents, and young adults.This study comprised 24,544 participants 6-24 years of age, with 33,506 medical observations made between 2000 and 2014. We used a spatiotemporal model to estimate PM2.5 concentrations at participants' addresses. Spirometry parameters, i.e., forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximum midexpiratory flow (MMEF), were determined. A generalized linear mixed model was used to examine the associations between long-term exposure to ambient PM2.5 and lung function. The odds ratios (ORs) of poor lung function were also calculated after adjusting for a range of covariates.Every 10-μg/m3 increase in the 2-y average PM2.5 concentration was associated with decreases of 2.22% [95% confidence interval (CI): -2.60, -1.85], 2.94 (95% CI: -3.36, -2.51), and 2.79% (95% CI: -3.15, -2.41) in the FVC, FEV1, and MMEF, respectively. Furthermore, it was associated with a 20% increase in the prevalence of poor lung function (OR: 1.20; 95% CI: 1.12, 1.29).Two-year ambient PM2.5 concentrations were inversely associated with lung function and positively associated with the prevalence of poor lung function in children, adolescents, and young adults in Taiwan. https://doi.org/10.1289/EHP5220.
Interventions to Enhance Adherence to Oral Antineoplastic Agents: A Scoping Review
Authors: Shoshana M Rosenberg, Keith J Petrie, Annette L Stanton, Lan Ngo, Emma Finnerty, Ann H Partridge
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background As new targeted oral antineoplastic therapies have emerged in recent years, the development of effective strategies that promote optimal adherence to cancer medication regimens has become an important priority. Methods We conducted a scoping literature review to search for English language articles published through July 15, 2019, to identify studies that reported the testing and/or evaluation of interventions to improve adherence to oral antineoplastic agents. Results A total of 56 articles were selected for review. Of the studies evaluated, 14 were randomized trials. All interventions except two targeted adult patients. Thirty-three studies enrolled fewer than 100 patients. Most interventions were education- and counseling-based and centered on provision of information about the drug and strategies to manage side effects. Only eight studies used an mHealth tool and/or text messages to target nonadherence. Among studies with a comparison sample, fewer than one-half (44.7%) reported statistically significant improvements in adherence or persistence associated with the intervention; however, some pharmacist-directed programs, particularly those that integrated monitoring or routine follow-up with a provider, did demonstrate efficacy. Conclusion Although the development of adherence-promoting interventions for oral antineoplastic therapies has increased recently, few have been rigorously tested. The nascent literature suggests those that are pharmacist directed and use regular monitoring show promise, though additional prospective studies are needed. Study methodology, population selection, and potential challenges that may be encountered in the implementation and dissemination phases should be considered when developing new interventions to address nonadherence to oral antineoplastic treatment.
Prognostic and diagnostic value of Ewing family of tumors (EFTs)-associated fusion transcripts detected in peripheral blood specimens.
Authors: Joanna Przybyl, Hanna Kosela, Katarzyna Wiater, Konrad Ptaszynski, Anna Szumera-Cieckiewicz, Slawomir Falkowski, Iwona A. Lugowska, Maria Debiec-Rychter, Janusz A Siedlecki, Piotr Rutkowski
Journal: Journal of Clinical Oncology (2012)

10538 Background: EFTs are characterized by chromosomal translocations leading to formation of oncogenic EWSR1-FLI1 fusion gene in 85-90% of cases. The aim of the study was to detect circulating tumor cells (CTCs) carrying EWSR1-FLI1 fusion transcript in peripheral blood and assess their added value to standard diagnostic procedures and utility as a prognostic marker in EFTs. Methods: 10mL of whole blood was collected from 35 untreated adult EFTs patients at the diagnosis (period: 2008-2011, median age 27 years) and 13 healthy controls. 13 patients presented metastatic disease (M1) at the diagnosis. Nested RT-PCR was applied in triplicate for the detection of EWSR1-FLI1 transcript. Blood specimen was regarded CTC-positive when at least 2 out of 3 nested RT-PCR assays were positive and results were confirmed by sequencing. FISH assay for EWSR1 rearrangement was performed on FFPE tumor tissue in 28 available cases. Median follow-up was 16 months. Results: EWSR1-FLI1 transcript was detected in peripheral blood of 71.4% (n=25) of patients. FISH assay was positive for EWRS1 rearrangement in 58% of cases. In 10 patients, where FISH assay could not be performed due to insufficient quality or lack of material, nested RT-PCR provided confirmation of immunopathological diagnosis. Specificity of RT-PCR blood test in healthy control was 91.4% (12/13 negative; p=0.0001). Median overall survival (OS) was 18 months. CTC-positive patients showed the trend for longer OS than CTC-negative patients (1-year OS: 89% vs. 58%; p=0.07), but longer follow-up is needed. Conclusions: Our results show that the fusion transcript detection in peripheral blood specimens may be a useful additional test to the standard clinicopathological diagnosis of EFTs. High detection rate of EWSR1-FLI1 transcript in peripheral blood of EFTs patients at the diagnosis may imply EFTs as a systemic disease with clinically evident metastases or micrometastases at presentation. Prognostic significance of CTCs in EFTs warrants further studies.
DDIS-18. NANOCELL-MEDIATED DELIVERY OF MIR-34A COUNTERACTS TEMOZOLOMIDE RESISTANCE IN GLIOBLASTOMA
Authors: Muhammad Babar Khan, Rosamaria Ruggieri, Nhan Tran, Jann Sarkaria, Jennifer MacDiarmid, Himanshu Brahmbhatt, John Boockvar, Marc Symons
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastomas show marked intra- and inter-tumor heterogeneity and are strongly resistant to both radio- and chemo-therapy, which are standard therapeutic modalities for this tumor. MicroRNAs (miRNAs) have the potential to serve as effective therapeutics for glioblastoma as they modulate the activity of multiple signaling pathways. METHODS Glioblastoma cultures were transfected with miR-34a or control miRNA mimics to assess biological function and therapeutic potential in vitro. miR-34a was packaged into bacterially-derived nanocells and administered intravenously for delivery to orthotopic patient-derived glioblastoma xenografts in mice. RESULTS Overexpression of miR-34a strongly reduced the activation status of the three core signaling networks that have been found to be deregulated in the vast majority of glioblastoma tumors, the receptor tyrosine kinase, p53 and Rb networks. miR-34a transfection also inhibited the survival of multiple established glioblastoma cell lines as well as primary patient-derived xenograft cultures representing the proneural, mesenchymal and classical subtypes. Transfection of miR-34a synergized with temozolomide (TMZ) in in vitro cultures of glioblastoma cells with primary TMZ sensitivity, primary TMZ resistance and acquired TMZ resistance. Intravenous administration of bacterially-derived nanocells carrying miR-34a strongly enhanced TMZ sensitivity in an orthotopic patient-derived xenograft mouse model of glioblastoma. CONCLUSIONS miR-34a strongly sensitizes a wide range of glioblastoma cell cultures to TMZ, suggesting that combination therapy of TMZ with miR-34a may serve as a novel therapeutic approach for the treatment of glioblastoma tumors. Bacterially-derived nanocells are an effective vehicle for the delivery of miR-34a to glioblastoma tumors.
Factors impacting decision by African American and underserved populations to choose active surveillance in early-stage prostate cancer.
Authors: Theresa Wicklin Gillespie, John Petros, Michael Goodman, Joseph Lipscomb, Laura Britan, Jessica Lauren Rowell, Lindsey Allison Herrel, Katharina V Echt
Journal: Journal of Clinical Oncology (2013)

5067 Background: African-American (AA) men have the highest rates of prostate cancer (PCa) incidence and mortality in the U.S. Screening for PCa with prostate specific antigen (PSA) has allowed detection of early stage disease, but side effects of radical prostatectomy and radiation raise concerns about unfavorable risk:benefit ratios of PSA screening and subsequent therapy. Active surveillance (AS) is an option for early-stage PCa (ESPC), but only 10% of men eligible for AS choose this approach. The 2011 NIH State-of-the-Science Conference promoted the need to enhance decision-making (DM) about AS. In 2012, the U.S. Preventive Services Task Force recommended against PSA screening, while encouraging patient DM. Our study examined DM needs by men (N=204; 68% AA; screening PSA within normal limits) and their significant others (SO) (N=181; 65% AA) regarding AS and other ESPC options. Methods: This multi-center, mixed methods study (N=402; 51% rural) included 5 sites nationwide. Subjects completed quantitative questionnaires prior to focus groups (FG); 54 FG were held, with separate groups for men and SO. Results: After adjusting for education, comorbidities, insurance, age, health literacy, distance to treatment center, willingness to travel, income and numeracy score, AA men were significantly more likely to be influenced by convenience (OR: 2.84, 95% CI: 1.42-5.65) compared to Caucasians. Rural residence, however, did not affect DM. In qualitative analysis, numerous themes were identified relevant to choice of AS: physician treatment discussions being limited to their own specialty; confusion due to conflicting sources of information; convenience; worry about untreated cancer remaining and treatment toxicities; and lack of awareness of AS as an option. SO tended to value cure over avoiding side effects. Conclusions: While the impact of new PCa screening guidelines is uncertain, for AS to become a viable treatment option, providers will need to discuss along with other therapeutic alternatives. SO are influential in DM and may be less enthusiastic about AS than men. For AA men, AS may be a particularly attractive option given the relative influence of convenience in DM.
Substrate curvature as a cue to guide spatiotemporal cell and tissue organization
Authors: Sebastien J.P. Callens, Rafael J.C. Uyttendaele, Lidy E. Fratila-Apachitei, Amir A. Zadpoor
Journal: Biomaterials (2019)

Recent evidence clearly shows that cells respond to various physical cues in their environments, guiding many cellular processes and tissue morphogenesis, pathology, and repair. One aspect that is gaining significant traction is the role of local geometry as an extracellular cue. Elucidating how geometry affects cell and tissue behavior is, indeed, crucial to design artificial scaffolds and understand tissue growth and remodeling. Perhaps the most fundamental descriptor of local geometry is surface curvature, and a growing body of evidence confirms that surface curvature affects the spatiotemporal organization of cells and tissues. While well-defined in differential geometry, curvature remains somewhat ambiguously treated in biological studies. Here, we provide a more formal curvature framework, based on the notions of mean and Gaussian curvature, and summarize the available evidence on curvature guidance at the cell and tissue levels. We discuss the involved mechanisms, highlighting the interplay between tensile forces and substrate curvature that forms the foundation of curvature guidance. Moreover, we show that relatively simple computational models, based on some application of curvature flow, are able to capture experimental tissue growth remarkably well. Since curvature guidance principles could be leveraged for tissue regeneration, the implications for geometrical scaffold design are also discussed. Finally, perspectives on future research opportunities are provided.
A Moving Meckel Diverticulum on 99mTc-Pertechnetate Imaging in a Patient With Inguinal Hernia
Authors: Yuan Zhang, Pei-qing Yang, Shun Li, Xiao-jia Cai, Shang-xu Yang
Journal: Clinical Nuclear Medicine (2019)

Abstract A boy aged 1 year 8 months underwent 99m Tc-pertechnetate scintigraphy to evaluate the cause of bloody stool. On the initial images, there was an abnormal activity in the right abdomen, which changed location to the right groin in later images. A Meckel diverticulum was identified by histopathology examination. We concluded this case of moving Meckel diverticulum was caused by the synergy between an inguinal hernia and high abdominal pressure.
Atopic dermatitis in the elderly
Authors: S. Williamson, J. Merritt, A. De Benedetto
Journal: British Journal of Dermatology (2020)

Atopic dermatitis (AD, also known as atopic eczema) is a chronic and relapsing skin disease, affecting over 230 million people worldwide. It commonly is seen in patients who have other allergic conditions including asthma and allergic rhinitis (hay fever) and is recognised by an itchy rash and dry irritated skin.
Targeted deletion of PD-1 in myeloid cells induces antitumor immunity
Authors: Laura Strauss, Mohamed A. A. Mahmoud, Jessica D. Weaver, Natalia M. Tijaro-Ovalle, Anthos Christofides, Qi Wang, Rinku Pal, Min Yuan, John Asara, Nikolaos Patsoukis, Vassiliki A. Boussiotis
Journal: Science Immunology (2020)

PD-1, a T cell checkpoint receptor and target of cancer immunotherapy, is also expressed on myeloid cells. The role of myeloid-specific versus T cell-specific PD-1 ablation on antitumor immunity has remained unclear because most studies have used either PD-1-blocking antibodies or complete PD-1 KO mice. We generated a conditional allele, which allowed myeloid-specific (PD-1f/fLysMcre) or T cell-specific (PD-1f/fCD4cre) targeting of Pdcd1 gene. Compared with T cell-specific PD-1 ablation, myeloid cell-specific PD-1 ablation more effectively decreased tumor growth. We found that granulocyte/macrophage progenitors (GMPs), which accumulate during cancer-driven emergency myelopoiesis and give rise to myeloid-derived suppressor cells (MDSCs), express PD-1. In tumor-bearing PD-1f/fLysMcre but not PD-1f/fCD4cre mice, accumulation of GMP and MDSC was prevented, whereas systemic output of effector myeloid cells was increased. Myeloid cell-specific PD-1 ablation induced an increase of T effector memory cells with improved functionality and mediated antitumor protection despite preserved PD-1 expression in T cells. In PD-1-deficient myeloid progenitors, growth factors driving emergency myelopoiesis induced increased metabolic intermediates of glycolysis, pentose phosphate pathway, and TCA cycle but, most prominently, elevated cholesterol. Because cholesterol is required for differentiation of inflammatory macrophages and DC and promotes antigen-presenting function, our findings indicate that metabolic reprogramming of emergency myelopoiesis and differentiation of effector myeloid cells might be a key mechanism of antitumor immunity mediated by PD-1 blockade.