tbuckley/cabot-search huggingface dataset:
Bridging the information gap: A scoping review of radiation oncology patient education scholarship.
Authors: David M. Rosenberg, Michael Kevin Rooney, Ritu Arya, Matthew J. Abrams, Steve E. Braunstein, Jennifer M. Croke, Meredith Elana Giuliani, Jillian Rebecca Gunther, Ariel Hirsch, Paris-Ann Ingledew, Sandra Turner, Daniel William Golden
Journal: Journal of Clinical Oncology (2019)

e23164 Background: Patient education (PE), the use of educational interventions to improve patient knowledge of healthcare, has been shown to reduce patient anxiety and facilitate shared decision making. In contrast to many other medical specialties, the state of radiation oncology (RO) PE is unclear. This scoping review aims to characterize the state of ROPE peer-review scholarship to describe strengths, identify gaps and guide future ROPE research. Methods: Predetermined medical subject headings and search terms were used to search PubMed for ROPE articles. Additional terms were identified from these articles and the search was repeated until no further articles were found. In-press articles in major RO and medical education (ME) journals were searched. English language articles published after 1/1/1990 that had a primary ROPE focus were included. Two independent reviewers performed the search and determined eligibility. Articles were categorized using the most predominant step of Kern’s six-step conceptual framework for ME curriculum development and the country and year of publication. Results: Of 11,756 identified articles, 182 met inclusion criteria. Articles per year increased over time (p &lt; 0.01): 1990-1994 (5.5%); 1995-1999 (11.0%); 2000-2004 (13.7%); 2005-2009 (10.4%); 2010-2014 (25.8%); 2015-2019 (33.5%). Conceptual framework categorization was as follows: problem identification (22.0%); needs assessment (23.6%); goals and objectives (4.9%); education strategies (9.9%); implementation (7.7%); evaluation and feedback (31.9%). Regional breakdown was as follows with some articles spanning regions: Africa (1.1%); South America (2.2%); Asia (6.0%); Australia (15.4%); Europe (30.2%); North America (45.6%). Conclusions: Nearly half of articles are primarily problem identification or needs assessment (45.6%) which are descriptive in nature and only identify or clarify ROPE needs. Additionally while these results are limited to English language scholarship, there are significant regional maldistributions. Although there is an encouraging trend of increasing ROPE publications over time, this study identifies opportunities to further develop, implement and evaluate ROPE scholarship.
PD-1 Blockade in a Liver Transplant Recipient With Microsatellite Unstable Metastatic Colorectal Cancer and Hepatic Impairment
Authors: Justin A. Chen, Naseem Esteghamat, Edward J. Kim, Gabriel Garcia, Jun Gong, Marwan G. Fakih, Richard J. Bold, May T. Cho
Journal: Journal of the National Comprehensive Cancer Network (2019)

Immune checkpoint inhibitors represent a newly established standard of care in patients with refractory metastatic colorectal cancer with mismatch repair deficiency and microsatellite instability. However, the use of immunotherapy is unclear in recipients of liver transplants with or without concurrent liver function abnormalities. Clinical trials investigating immunotherapy have mostly excluded liver transplant recipients and patients with abnormal liver function. This report presents the first case, to our knowledge, of a liver transplant patient with mismatch repair–deficient colon adenocarcinoma with liver metastases and concurrent abnormal liver function who safely responded to immunotherapy. We also review the literature on checkpoint inhibitor use in patients with other metastatic solid tumors after liver transplant and those with baseline liver function abnormalities. An increasing body of evidence supports the safety of checkpoint inhibition in patients with cancer and solid organ transplants, but further prospective studies are warranted. Use of immunotherapy in liver transplant recipients who have metastatic colorectal cancer with microsatellite instability is feasible but should be performed in a multidisciplinary team setting.
Use of CD30 expression in human malignant mesothelioma as a novel therapeutic target.
Authors: Afshin Dowlati, Snehal Dabir, Adam Kresak, Michael Yang, Gary Wildey
Journal: Journal of Clinical Oncology (2013)

e18526 Background: CD30 antigen is important in the diagnosis of Hodgkin’s disease (HD) and anaplastic large cell lymphoma (ALCL). CD30 is a cytokine receptor that belongs to the tumor necrosis factor superfamily (TNFRSF8) and acts as a positive regulator of apoptosis. The expression of CD30 in malignant mesothelioma is unknown. Given the remarkable success of brentuximab vedotin, an antibody-toxin conjugate directed against CD30 antigen, in treating patients with relapsed HD and ALCL, we undertook a study to validate the incidence of CD30 expression in mesothelioma and to examine its clinical correlates. Furthermore, we performed studies using cultured mesothelioma and non-small cell lung cancer (NSCLC) cell lines to determine the expression and potential targeting of CD30 antigen in vitro. Methods: Patient mesothelioma tissue specimens (n=52) were examined for CD30 expression by immuno-histochemistry (IHC) with an anti-BerH2 antibody (Cell Marque) used for the diagnosis of HD. Staining was assessed by a thoracic pathologist. Mesothelioma (H28, H2052, H2452, 211H) and NSCLC (A549, H1299) cell lines were also grown in culture and examined for CD30 expression by FACS analysis and confocal microscopy using anti-CD30 antibody (Novus Biologicals). Cells were permeabilized with Triton X-100. Results: Positive CD30 expression was noted in six out of 52 total mesothelioma specimens. Five of the six positive tumors demonstrated epithelial histology and were scored as low or intermediate grade. Membrane-associated as well as diffuse cytoplasmic staining was observed. The percentage of tumor cells stained positive varied greatly. Interestingly, no high grade epithelial tumors were scored as CD30 positive. The remaining CD30 positive tumor was a high grade, biphasic metastatic tumor. Confocal analysis of both mesothelioma cultured cells localized CD30 antigen to the cell membrane. Flow cytometry of intact and permeabilized mesothelioma cells supported the idea that CD30 antigen was located on the cell-surface. Conclusions: Our studies validate the presence of CD30 antigen on the cell surface of epithelial-type mesothelioma and indicate that selected mesothelioma patients may derive benefit from brentuximab vedotin (Adcetris).
Co-benefits of sustainable farming methods to safeguard food security and environmental health in China: a modelling study
Authors: Amos P K Tai, Ka Ming Fung, Hon-Ming Lam, Taiwen Yong, Xiaoming Liu
Journal: The Lancet Planetary Health (2019)

BackgroundModernised farming has contributed significantly to the increased global food supply over the past half-century, albeit while creating severe threats to the environment. Excessive application of chemical fertiliser has in particular led to massive release of reactive nitrogen compounds into the atmosphere, where they become major components of fine particulate matter (PM2·5) pollution, with detrimental effects on human health. Various sustainable farming methods with lower environmental impacts have been experimented with and practised in many countries, but their wider benefits beyond the farm scale have rarely been examined. One such method is intercropping with soybeans, which takes advantage of the nitrogen fixing ability of soybeans to improve nutrient use efficiency and reduce fertiliser use.MethodsWe developed a computational modelling framework using the GEOS-Chem and DNDC models, revising the representation for soil nitrogen processes and crop-crop interaction. We did model experiments to quantify the benefits of nationwide adoption of maize-soybean intercropping systems in China in terms of gains in crop production, decreases in fertiliser consumption, and reductions in ammonia (NH3) emissions. We further examined how the decline in NH3 emissions could reduce the downwind formation of PM2·5 and the associated public health costs.FindingsAnnual mean PM2·5 concentrations can be reduced by up to 1·5 μg/m3 with the nationwide adoption of maize-soybean intercropping, with a corresponding annual net economic benefit of US$67 billion, of which $13 billion arises from saved health costs from reduced air pollution.InterpretationOur study shows the wider economic and environmental value of intercropping systems for promoting both food security and public health, serving as a basis for policy consideration by governments and stakeholders. The same modelling framework can likewise be used to investigate the large-scale impacts of other sustainable farming methods.FundingGeneral Research Fund the Hong Kong Research Grants Council, the Area of Excellence Scheme, and the CUHK Vice- Chancellor Discretionary Fund.
Genetic polymorphisms in the Paraoxonase 1 (PON1) gene and the risk of ovarian epithelial carcinoma
Authors: Galina Lurie, Lynne Wilkens, Pamela Thompson, Katharine McDuffie, Michael Carney, Keith Terada, Marc Goodman
Journal: Cancer Research (2008)

1909  Background: An elevated oxidative stress has been found to play an important role in the pathogenesis of cancer. The antioxidant paraoxonase (PON1) is an endogenous free radical scavenger that can inhibit tumor cell proliferation. PON1 gene has 2 common coding polymorphisms (SNPs): rs662 in exon 6 (Gln192Arg) and rs854560 in exon 3 (Leu55Met). Both SNPs have been shown to influence PON1 activity. We investigated association of these SNPs with the risk of epithelial ovarian carcinoma. We also explored whether smoking, which is known to decrease PON1 activity, modified this association.  Methods. Interviews and DNA samples were collected in a population-based case-control study of 364 women with epithelial ovarian carcinoma and 602 controls frequency-matched to cases on age and ethnicity. Genotyping was performed with the 5’ nuclease discrimination assay using TaqMan (Applied Biosystems). Samples from cases and controls were intermixed on each plate, and 144 (7.4%) randomly selected blinded were included to evaluate accuracy and reproducibility. The concordance rates among duplicates were 100% for both SNPs. Call rates were 99% and 100% for rs662 and rs854560, respectively. Unconditional logistic regression was used to test the associations between SNPs and ovarian cancer risk, while adjusting for potential confounders.  Results. The distributions of the alleles among control subjects were consistent with Hardy-Weinberg equilibrium. We found that the rs854560 T allele was associated with a lower risk of ovarian cancer among Caucasian, Japanese, Hawaiian, Filipino women, and all women combined (OR=0.52; 95% CI:0.36-0.76 ; p global=0.0006; p for gene-dose effect =0.003) when compared to homozygous carriers of A allele. The interaction between this SNP and smoking exposure on risk was not statistically significant. However, among smokers, risk asociated with AA genotype was considerably higher (OR=2.42; 95%CI:1.39-4.25) than among non-smokers (OR=1.68; 95%CI:1.02-2.77). There was no evidence for effect modification of this SNP association with risk by in utero or second-hand tobacco exposure. Association of rs662 T allele with reduced risk was consistent among ethnic groups but was not statistically significant.  Conclusion. In our study, women carriers of rs854560 T allele were at significant 48% decrease in ovarian cancer risk when compared to AA genotype carriers. Increased risk associated with AA genotype was considerably higher in past or current smokers when compared to women who never smoked. The biological plausibility of our findings is supported by the evidence for higher paraoxonase activity levels in T allele carriers and weakening of the antioxidant defense of PON1 by smoking.
P09.07 Constitutive activation of the EGFR-STAT1 axis increases proliferation of meningioma tumour cells
Authors: C O Hanemann, S Ferluga, D Baiz, V Sharma, C L Adams, K Bassiri, J Dunn, E Ercolano, K Kurian, D A Hilton
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Meningiomas are the most frequent primary brain tumours of the central nervous system. The standard of treatment is (radio)surgery, but the lack of knowledge of their tumorigenesis contributes to delay the development of additional therapeutic options. MATERIAL AND METHODS We used a variety of differen model systems and cell biology techniques RESULTS We found STAT1 widely overexpressed in meningioma tumours and in patient-derived meningioma cells but not in the corresponding healthy controls. The protein showed a constitutive phosphorylation on both phosphosites (Y701 and S727), which was not dependent on the JAK/STAT pathway. STAT1 knocked down resulted in a significant reduction of cellular proliferation, showed as a decrease in Ki67-positive cells and Cyclin D1, and deactivation of AKT and ERK 1/2. By studying STAT1 binding partners we isolated a complex composed by STAT1, STAT2, PRMT5 and MEP50. As PRMT5 is known to interact with EGFR, we tested the tyrosine kinase and found that EGFR was constitutively active in meningioma and was responsible for the aberrant phosphorylation of STAT1 on both phosphosites. We tested different drugs inhibiting of EGFR phosphorylation, Canertinib was most effective. It caused a significant reduction in meningioma cells proliferation and a reduction of overall levels of Cyclin D1, phospho- AKT and phospho-ERK 1/2. Hence, STAT1 constitutive phosphorylation, initiated by EGFR activation, is responsible for inducing a positive feedback loop causing its own overexpression and consequently an increased proliferation of the tumour cells. CONCLUSION These findings underline a pivotal role of the EGFR and STAT1 axis in meningioma and provides the rationale for further studies aiming to identify novel and effective therapeutic options.
Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection
Authors: Allison N. Bucşan, Ayan Chatterjee, Dhiraj K. Singh, Taylor W. Foreman, Tae-Hyung Lee, Breanna Threeton, Melanie G. Kirkpatrick, Mushtaq Ahmed, Nadia Golden, Xavier Alvarez, James A. Hoxie, Smriti Mehra, Jyothi Rengarajan, Shabaana A. Khader, Deepak Kaushal
Journal: Journal of Clinical Investigation (2019)

HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in HIV-coinfected individuals.
Progressive increasing in the risk of second and subsequent malignant tumors in patients with a head and neck cancer: A validation study with SEER data.
Authors: Xavier Leon, Antonio Lopez-Pousa, J Carlos Villatoro, Miquel Quer, Ivana Sullivan, Paola Murata, Agostina Stradella, Josep M. De Vega, Nuria Farre, Oscar Gallego Rubio, Maria Jesus Quintana, Agust Barnadas, Milagros Alonso Martinez
Journal: Journal of Clinical Oncology (2012)

5595 Background: Patients with a head and neck squamous cell carcinoma (HNSCC) index tumor have a increased risk (2-4% per year) for appearance of a second malignant neoplasms (SMN) and higher risk for successive malignant tumors during the follow-up. The objective of our study was to validate this concept with data of patients included in the Surveillance Epidemiology and End Results (SEER) program (1973-2008). Methods: We performed a population-based cohort study of 149.328 patients with a primary oral cavity, oropharynx, hypopharynx and larynx squamous cell carcinoma index tumor, included in the SEER program, to analize the actuarial survival-free of second and successive tumors. A total of 11.948 (8%) patients had one or more malignant tumors before the diagnosis of HNSCC. Results: During the follow-up period, a total of 31.507 new SMN appeared. There was a progressive and significant increase in the risk of SMN. The annual hazard ratio for 2nd to 7th successive SMN was 2.3%, 2.7%, 3.9%, 5.4%, 8.9% and 19.1% annual risk respectively. Additionally 11 patients had 8th SMN. We observed a progressive increase in the risk of appearence of new malignant tumors located in and outside the aerodigestive tract. The increase in the risk of SMN was higher for tumors located in the aerodigestive tract than tumors located outside aerodigestive tract. It was a tendency towards the increase in the proportion of HNSCC with the appearance of new tumors, with a decrease in the proportion of the malignant tumors located in the lung and in locations outside the aerodigestive tract. There were significant differences inthe risk of SMN between second and third, third and fourth, fourth and fifth, and sist and seventh tumors (p&lt;0.0001). Conclusions: In patients with HNSCC there is a progressive increase in the risk of appearance of successive tumors. Previous tobacco and alcohol consumption, persistence in the exposure to carcinogens and individual susceptibility (genetic) could play a role in the increased risk of SMN. We have validated this concept with data from the SEER program.
Religion index for psychiatric research
Authors: H Koenig, G R Parkerson, K G Meador
Journal: American Journal of Psychiatry (1997)

In a project conducted at the Medical Center of Central Massachusetts, in conjunction with the Massachusetts Department of Mental Health, board-certified psychiatrists interviewed patients over a video link regarding suicidal ideation, imminent suicidal intent, homicidal ideation or intent, active delusions, hallucinations, or gross impairment of judgment.Ratings on multiple scales, which culminated in determination of the need for involuntary commitment, were independently completed by a psychiatrist in the room with the patient and the interviewer at the remote telemedicine site.In 12 evaluations, the mean weighted kappa coefficient for the two raters on the eight clinical scales was 0.85 (F=20.85,df=95, 95, p<0.001).According to the criteria of Landis and Koch (3), this result indicates "very good" agreement between raters.For determining the need for involuntary commitment, there was perfect agreement between raters (kappa= 1.00); 50% of the patients met the Massachusetts commitment criteria.After the evaluations, the "in room" psychiatrist conferred with the telepsychiatrist regarding additional information that might have been observed directly but missed by the video link; in none of the 12 evaluations was such an omission noted.On the basis of this experience and the ongoing monitoring of telemedicine evaluations by videotaping (with patient consent), we have established a system for the telemedicine evaluation of patients at multiple participating facilities.We believe this model both improves the quality of emergency care available to satellite facilities and greatly reduces the cost of this critical service.
Perinatal Outcomes in Medicaid Expansion and Nonexpansion States Among Hispanic Women
Authors: Diana Montoya-Williams, Heather Burris, Elena Fuentes-Afflick
Journal: JAMA (2019)

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hTert, MMP1, Her2 expressions by preneoplastic lesions and breast cancer risk
Authors: J. Hernandez, M. Mathieu, E. Taranchon, M. Spielmann, S. Delaloge, J. Soria, F. André
Journal: Journal of Clinical Oncology (2006)

10510 Background: Although it is well established that preneoplastic lesions are associated with an increased risk of breast cancer, there is no available tool to identify which patients will develop breast cancer. Telomerase, matrix metalloprotease 1 (MMP1) and Her2 have all been involved in the early steps of carcinogenesis. In the present study, we have looked at whether the expression of hTert, MMP1 and her2 in preneoplastic lesions were associated with higher risk of breast cancer. Methods: hTert, MMP1 and Her2 expressions by preneoplastic lesions were determined by immunohistochemistry in 34 patients who have subsequently developed a breast cancer (cases), and in 32 patients who did not present breast cancer in the follow-up (control). Patients were matched for age, length of follow-up and type of preneoplastic lesion. The expression of the three biomarkers was compared in the two groups. The initially planned sample size of the study was 90 matched patients, but only 66 samples could be proceed for technical reasons. Results: Median age was 47 and 49 years old in patients with and without further cancer respectively. In the group of patients who subsequently developed breast cancer (cases), preneoplastic lesions consisted in lobular hyperplasia or lobular in situ carcinoma in 17 cases, ductal atypical hyperplasia in 12 cases and mixed lesions in 5 cases. In the control group, preneoplastic lesions consisted in lobular hyperplasia or lobular in situ carcinoma in 18 cases, ductal atypical hyperplasia in 12 cases, mixed lesions in 2 cases. The median interval between the diagnosis of preneoplastic lesion and the occurrence of breast cancer was 72 months (17–291). hTert was expressed in 8 (27%) and 2 (7%) assessable lesions in cases and controls respectively (p = 0.04). MMP1 was expressed in 21 (65%) and 22 (73%) assessable lesions in cases and control respectively (p = 0.49). Her2 was expressed in 6 preneoplastic lesions both in cases and controls (20%). Conclusions: This study suggests that hTert expression by preneoplastic lesions could be associated with an increased risk breast cancer. No significant financial relationships to disclose.