tbuckley/cabot-search huggingface dataset:
Can abdominal ultrasound replace CT scanning in long-term follow-up of male patients with germ cell tumor?
Authors: Arthur Gerl, Adina Hauck, Marcus Hentrich
Journal: Journal of Clinical Oncology (2012)

4602 Background: To date, there is no international consensus on how best to follow patients (pts) with GCT after their initial management. In the absence of a generally accepted follow-up schedule the possible benefits of regular CT scanning must be weighed against their cost, potential contrast media reactions and the long term risk of cumulative X-ray exposure. The present study focuses on the role of abdominal ultrasound in the follow-up of males with GCT and raises the question whether CT-scanning may be replaced by abdominal ultrasound. Methods: This retrospective single-center cohort study included 887 GCT pts followed between January 2001 and November 2011. The follow-up schedule was predominately based on abdominal ultrasound performed by the same physician (A.G.). Patterns of recurrence and the long-term outcome were analyzed. Results: 462 of 887 pts (52.1%) had stage I, 258 (29.1%) stage II and 130 (14.7%) stage III disease (not evaluable in 37 pts). The median time between baseline and the most recent follow-up examination was 5.0 years. A total of 14.604 abdominal ultrasound examinations (16.5/pt.), 1170 CT scans (1.32/pt.), and 956 chest X-rays (1.08/pt) were performed. A relapse occurred in 58 pts (6.5%) with 11 of 58 pts experiencing multiple relapses. 34 of 58 relapses (58.6%) were detected in pts with stage I GCT. The sites of relapse included the abdomen (n=42), other sites (n=10), and marker elevation only (n=10). 33 of 42 abdominal relapses (78.6%) were detected by abdominal ultrasound. The median size of abdominal lymph nodes was 25 mm (range, 6 - 67 mm). After a median follow-up of 5 years the GCT specific survival of the entire cohort was 98.4%. Regarding the subgroup of pts with relapse the GCT specific survival was 94.7%. Conclusions: Ultrasound appears to be an appropriate method to detect abdominal recurrences in pts with GCT. However, training and cumulative experience is necessary to detect retroperitoneal recurrences at an early stage. The number of expensive and potentially harmful CT scans may be markedly decreased by abdominal ultrasound.
Abstract #995: Comparability of two control groups in a case-control study of infant leukemia: A Report from the Children\#8217;s Oncology Group (COG)
Authors: Susan Puumala, Logan Spector, Leslie Robison, Amy Linabery, Michelle Roesler, Julie Ross
Journal: Cancer Research (2009)

Careful control selection in case-control studies is important for obtaining unbiased estimates of relative risk. Traditionally, controls in pediatric cancer studies in the COG have been selected through random digit dialing (RDD). However, due to rapidly declining participation rates and lack of information on non-participants, RDD controls are no longer considered efficient or methodologically-sound. An alternative to RDD is birth certificates (BC), since they are population-based and can offer data to help characterize nonparticipants. We examined controls collected for a case-control study of infant leukemia in the COG using the two different approaches (RDD: 5/1999-10/2002 and BC: 10/2003-3/2008). Demographic factors of each group were compared to each other and both were compared to a national sample of U.S. births. Analysis was performed using chi-square tests for categorical variables and t-tests for continuous variables. For RDD controls, 25,516 telephone numbers were selected, of which 11,713 were verified to be residential; of these, 3,638 could not be screened, 7,394 had no eligible children, and 253 refused screening. A total of 430 were screened households with eligible children. Maternal interviews were completed for 255 of eligible screened controls. BC controls (n=270) were identified from 15 states that registered the largest number of infant leukemia cases. A total of 120 mothers were not found, 21 passively refused, 55 actively refused, 3 were not eligible, 1 partially completed the interview, and 70 completed the interview. The 255 RDD and 70 BC controls were not statistically significantly different with regards to maternal factors (age, race, education, marital status, and alcohol during pregnancy) or child factors (sex, gestational age, birth weight), but were different in reported smoking during pregnancy (22% RDD, 12% BC; p= 0.05). Both control groups differed significantly from U.S. births. Mothers of our controls were more likely to be older (29.8 vs. 27.2 years), white (84% vs. 59%), married (85% vs. 67%), have over 16 years of education (37% vs. 25%), and to report smoking (20% vs. 12%) and drinking (21% vs. 1%) during pregnancy compared to national birth data (all p-values   Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 995.
Herceptin-conjugated paclitaxel loaded PCL-PEG worm-like nanocrystal micelles for the combinatorial treatment of HER2-positive breast cancer
Authors: Jiahui Peng, Juan Chen, Fang Xie, Wei Bao, Hongyan Xu, Hongxia Wang, Yuhong Xu, Zixiu Du
Journal: Biomaterials (2019)
Cross-linking of the human DNA repair protein O6-alkylguanine DNA alkyltransferase to DNA in the presence of 1,2,3,4-diepoxybutane and antitumor nitrogen mustards.
Authors: Rachel Loeber, Danae Quirk Dorr, Melissa Goggin, Anthony E. Pegg, Natalia Tretyakova
Journal: Cancer Research (2006)

5244  O6-alkylguanine DNA alkyltransferase (AGT) repairs O6-alkylguanine lesions in DNA by direct transfer of the O6-alkyl group to an active site cysteine (Cys145), restoring normal guanine and preventing mutagenesis. However, previous studies suggested that AGT expression increased the cytotoxic and mutagenic effects of several bis-electrophiles, including 1,2,3,4-diepoxybutane (DEB) and antitumor nitrogen mustards (NM). Because these bifunctional alkylating agents produce N7-guanine monoadducts that retain one of the electrophilic groups, they are likely to induce DNA-protein cross-links by interacting with nucleophilic residues within AGT. The purpose of this study was to determine the structures of DEB- and NM-induced AGT-DNA conjugates and to identify specific amino acid residues involved in cross-linking. DNA-protein cross-link formation was detected by SDS-PAGE when 32P-labeled double-stranded oligodeoxynucleotides were exposed to DEB in the presence of either wild-type hAGT or a C145A hAGT mutant lacking the alkyl acceptor residue. Capillary HPLC-ESI+ mass spectrometric analysis of hAGT that had been incubated with N7-(2’-hydroxy-3’,4’-epoxybut-1’-yl)-deoxyguanosine (dG monoepoxide) or N7-guanine-half mustards of mechlorethamine and chlorambucil revealed the ability of the protein to form either one or two cross-links to dG. The cross-link locations were mapped to Cys145 and Cys150 by HPLC-ESI+-MS/MS analyses of tryptic digests. The same two active site residues participated in cross-linking following the incubation of hAGT with double-stranded DNA in the presence of DEB, mechlorethamine, and chlorambucil. The exact chemical structures of the cross-linked lesions were established as 1-(S-cysteinyl)-4-(guan-7-yl)-2,3-butanediol (Cys-Gua-BD), N-(2-[S-cysteinyl]ethyl)-N-(2-[guan-7-yl]ethyl)methylamine (Cys-Gua-EMA), and N-(2-[S-cysteinyl]ethyl)-N-(2-[guan-7-yl]ethyl)-p-aminophenylbuyric acid (Cys-Gua-PBA) by HPLC-ESI+-MS/MS analysis of the amino acids resulting from total digestion of modified proteins analyzed in parallel with synthetic standards. DNA-protein cross-linking is a likely mechanism for cytotoxicity and mutagenicity of DEB and NM in cells expressing AGT protein.
A "fact of the matter" may not exist in scientific narratives such as serotonin and depression
Authors: P. J. Cowen
Journal: BMJ (2015)

Healy’s observations on serotonin and depression make interesting, if familiar, reading.1 2 However, I was struck by the remarkable claim that the focus on serotonin has led to the “eclipse of cortisol” in mood disorder research. A quick search in Scopus with “cortisol” and “depression” …
Oncogenic KrasG12D and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas
Authors: Kamel Izeradjene, Chelsea Combs, Melissa Best, Aarthi Gopinathan, Amary Wagner, William Grady, Chu-Xia Deng, Ralph Hruban, Volkan Adsay, David Tuveson, Sunil Hingorani
Journal: Cancer Research (2007)

LB-80  Physiologic expression of oncogenic Kras initiates pancreatic tumorigenesis, while subsequent genetic events define the clinical and histopathologic features of the resultant disease. Distinct histopathologic routes to infiltrating pancreatic ductal adenocarcinoma (PDA) have been described with profoundly different prognoses for patients despite possessing overlapping mutational spectra. Invasive disease can arise from pancreatic intraepithelial neoplasias (PanINs), the most common pancreatic precursor lesion, as well as from two distinct classes of cystic neoplasia, intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs). We show here that concomitant expression of KrasG12D and haploinsufficiency of the Smad4/Dpc4 tumor suppressor gene results in the development of MCNs. These MCNs arise primarily in the body and tail of the organ and manifest an “ovarian-type” stroma, consisting of focally dense collections of PR-positive and ER-positive cells. The murine MCNs progress through discrete histologic stages, accompanied by LOH of Dpc4 and mutation of either p53 or p16, and culminate in invasive adenocarcinomas, faithfully recapitulating the human disease. This phenotype contrasts dramatically with engineered mutation of either the Trp53 or p16/Ink4a pathways in the setting of targeted KrasG12D expression, in which murine PanINs progress to invasive PDA with distinct biological sequelae. Thus, our findings elucidate an MCN-to-PDA progression scheme analogous to, but distinct from, the classical PanIN-to-PDA sequence and may help explain the dramatically different prognoses for these two pathways to invasive disease. In primary pancreatic carcinoma cell lines with mutation of Trp53 but intact Smad4, TGFβ induces dramatic epithelial-to-mesenchymal transition (EMT) and stimulates cellular migration. Conversely, primary cells from invasive MCNs lacking Smad4/Dpc4 were resistant to these effects, which may also help explain the lower frequency of metastatic lesions and improved survival seen in this setting. That the same overall mutational spectra are encountered in both of these distinct phenotypic routes to invasive adenocarcinoma of the pancreas also suggests that the sequence, as well as the context, in which these critical mutations are acquired helps determine the ensuing pathology.
Variation in Practice Patterns and Reimbursements Between Female and Male Urologists for Medicare Beneficiaries
Authors: Catherine S. Nam, Akanksha Mehta, Jessica Hammett, Frances Y. Kim, Christopher P. Filson
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Previous assessments of practice patterns and reimbursements for female urologists relied on surveys or board certification logs. A current evaluation of the geographic distribution and practice patterns by female urologists would reveal contemporary patterns of access for Medicare beneficiaries. <h3>Objective</h3> To characterize the variation in practice patterns and reimbursements by urologist sex and the regional deficiencies in care provided by female urologists. <h3>Design, Setting, and Participants</h3> This population-based cohort study used the publicly available Centers for Medicare &amp; Medicaid Services Provider Payment database to evaluate payments for US urologists. The cohort (n = 8665) included urologists who provided and were paid for 11 or more services to Medicare beneficiaries in 2016. Data collection and analysis were performed from October 3, 2018, through June 19, 2019. <h3>Main Outcomes and Measures</h3> Proportion of female-specific services, payments per beneficiary, and payments per work relative value unit (wRVU) by urologist sex were assessed. Density of female urologists across hospital markets was also identified. <h3>Results</h3> Among the 8665 urologists who received payments in 2016, 7944 (91.7%) were men and 721 (8.3%) were women. Female urologists, compared with male urologists, saw a lower proportion of patients with cancer (mean [SD], 16.3% [9.2%] vs 22.7% [8.8%];<i>P</i> &lt; .001) and a greater proportion of female Medicare beneficiaries (mean [SD], 52.8% [23.2%] vs 24.4% [10.3%];<i>P</i> &lt; .001). Female urologists generated a greater proportion of wRVU from urodynamics (median [IQR], 2.88% [1.26%-4.84%] vs 1.07% [0.31%-2.26%];<i>P</i> &lt; .001) and gynecological operations (median [IQR], 0.68% [0.45%-1.07%] vs 0.41% [0.20%-0.81%];<i>P</i> &lt; .001) than male urologists. In addition, female urologists, compared with their male counterparts, received lower median payments per beneficiary seen ($70.12 [interquartile range (IQR), $60.00-$84.81] vs $72.37 [IQR, $59.63-$89.29];<i>P</i> = .03) and lower payments per wRVU ($58.25 [IQR, $48.39-65.26] vs $60.04 [IQR, $51.93-$67.88];<i>P</i> &lt; .001). One-third (103 [33.7%]) of 306 hospital referral regions had 0 female urologists, and 80 (26.1%) had only 1 female urologist. <h3>Conclusions and Relevance</h3> Female urologists were more likely to provide care for female Medicare beneficiaries, to receive lower payments per wRVU generated and beneficiaries seen, and to be difficult to access in certain geographic areas; these findings have policy-related implications and highlight the regional deficiencies in urological care and reimbursement discrepancies according to urologist sex.
Therapeutic Potential of AO-176, a Next Generation Humanized CD47 Antibody, for Hematologic Malignancies
Authors: W. Casey Wilson, Myriam N Bouchlaka, Ben J Capoccia, Ronald R Hiebsch, Michael J Donio, Robyn J Puro, Alun J Carter, Prabir Chakraborty, Pamela T Manning, Robert W Karr, Vicki Sung, Daniel S Pereira
Journal: Blood (2018)
Evaluation of the Cascade of Diabetes Care in the United States, 2005-2016
Authors: Pooyan Kazemian, Fatma M. Shebl, Nicole McCann, Rochelle P. Walensky, Deborah J. Wexler
Journal: JAMA Internal Medicine (2019)

Treatment advances in diabetes can meaningfully improve outcomes only if they effectively reach the populations at risk.To evaluate whether the cascade of US diabetes care, defined as diabetes diagnosis, linkage to care, and achievement of individual and combined treatment targets, improved from 2005 to 2016 and to investigate potential disparities in US diabetes care.Nationally representative, serial cross-sectional studies included in the 2005-2016 National Health and Nutrition Examination Survey were evaluated. Data on nonpregnant US adults (age ≥18 years) with diabetes who had reported fasting for 9 or more hours (n = 1742 diagnosed and 746 undiagnosed) were included. Data analysis was performed from August 1, 2018, to May 10, 2019.Time period (2005-2008, 2009-2012, and 2013-2016), age, sex, race/ethnicity, health insurance, and educational level incorporated into logistic regression models predicting odds of target achievement.Proportion of participants overall and stratified by age, sex, and race/ethnicity who were linked to diabetes care and met glycemic (hemoglobin A1c <7.0%-8.5%, depending on age and complications), blood pressure (<140/90 mm Hg), cholesterol level (low-density lipoprotein cholesterol <100 mg/dL), and smoking abstinence targets and a composite of all targets.In 2013-2016, of 1742 US adults with diagnosed diabetes, 94% (95% CI, 92%-96%) were linked to diabetes care; 64% (95% CI, 58%-69%) met hemoglobin A1c level, 70% (95% CI, 64%-75%) met blood pressure level, and 57% (95% CI, 51%-62%) met cholesterol level targets; 85% were nonsmokers (95% CI, 82%-88%); and 23% (95% CI, 17%-29%) achieved the composite goal. Results were similar in 2005-2008 (composite 23%) and in 2009-2012 (composite 25%). There was no significant improvement in diagnosis or target achievement during the study period. Compared with middle-aged adults (45-64 years) with diagnosed diabetes, older patients (≥65 years) had higher odds (adjusted odds ratio [aOR], 1.70; 95% CI, 1.17-2.48) and younger adults (18-44 years) had lower odds (aOR, 0.53; 95% CI, 0.29-0.97) of meeting the composite target. Women had lower odds of achieving the composite target than men (aOR, 0.60; 95% CI, 0.45-0.80). Non-Hispanic black individuals vs non-Hispanic white individuals had lower odds of achieving the composite target (aOR, 0.57; 95% CI, 0.39-0.83). Having health insurance was the strongest predictor of linkage to diabetes care (aOR, 3.96; 95% CI, 2.34-6.69).It appears that the diabetes care cascade in the United States has not significantly improved between 2005 and 2016. This study's findings suggest that gaps in diabetes care that were present in 2005, particularly among younger adults (18-44 years), women, and nonwhite individuals, persist.
Assessment of knowledge, attitude and practice and associated factors towards palliative care among health care providers to the pediatric oncology patients in southern Philippines.
Authors: Jayson Cagadas Pasaol
Journal: Journal of Clinical Oncology (2019)

e21536 Background: Palliative care (PC) aims to prevent, relieve and manage the symptoms of cancer and the adverse effects of cancer treatment; however, lack of education is among the biggest challenges facing PC in Philippines. Education and Awareness are dismal, especially in Southern Philippines. This study aimed to assess the level of knowledge, attitude, and practice of Health Care Provider towards pediatric PC. And to discover associated factors that limits the pediatric oncology patients to receive PC and identify the barriers in providing PC by the cancer centers to the pediatric oncology patients. Methods: A cross-sectional study design, conducted at tertiary care hospital that offers PC to pediatric oncology patients at Southern Philippines. Structured questionnaire was circulated to identify the barriers of PC, and assess the Knowledge, Attitude and Practices (KAP) of health care provider using a systematic random sampling method. The data was entered, cleaned and analyzed using excel and SPSS version 19.0 software. The chisquare test was employed to assess the association between variables. A p-value of less than 0.05 was considered as statistically significant. Results: From the total of 508 health care providers selected, a response rate of 500 (98.4%) were registered. Among the respondents 287(57.4%) had good knowledge and 259 (58.1%) had favorable attitude towards pediatric PC. In contrast, the level of practice showed that the majority 384 (76.8%) of health care providers had poor practice towards PC. Results showed that 94% to 99% of health care providers believed that the inadequate research evidence base to guide and measure the quality of life and lack of staff training in pediatric PC were the major barriers in providing PC by the cancer centers to the pediatric oncology patients. And 100% health care providers affirmed that the ignorance and lack of awareness about the existing program and resources of PC were the major factors that limits the pediatric oncology patients to receive pediatric PC in Southern Philippines. Conclusions: The health care providers had poor training and knowledge aspect of practice, but their attitude towards PC was favorable. Recommendations are the needs to be incorporated in the Department of Health through Continuing Professional Development to promote regular training for PC. Also, Educational awareness to assist healthcare professionals and pediatric oncology patients involved in PC needs to be regulated and provide.
ESA Resistance May Be a Potential Confounder for Mortality among Different ESA Types
Authors: Mototsugu Tanaka, Kayo Shinohara, Akiko Ono, Mutsuhiro Ikuma
Journal: Journal of the American Society of Nephrology (2019)

Today, it is well known that patients with CKD with erythropoiesis-stimulating agent (ESA)–resistant renal anemia have a poorer prognosis than those without ESA-resistant renal anemia.1 Sakaguchi et al.2 reported that patients treated with long-acting ESA showed higher mortality rates than those with short-acting ESA after adjusting patient characteristics. This raises a critical question whether widely used long-acting ESA per se has some adverse effects on the prognosis of patients with CKD. In their study, patients were divided into the first to the third tertile according to ESA doses, and all-cause mortality in the same tertile was compared between long-acting and short-acting ESA. As ESA doses increased up to the third tertile, the adjusted hazard ratio for all-cause mortality in long-acting ESA users became significantly worse than that in short-acting ESA users. However, we are concerned about the appropriateness of this approach because it is difficult to interpret the results obtained from ESAs with different pharmacodynamics. Although the authors calculated the ESA resistance index from ESA doses, hemoglobin level, and body weight, a conversion ratio such as epoetin alfa/beta (EPO) to darbepoetin alfa (DA) should be taken into consideration. It has been reported that 1 μg of DA is equivalent to 200 U of EPO (EPO/DA ratio =200),3 whereas in their study, the EPO/DA ratio was 163, 167, and 136 in the first, second, and third tertile, respectively. This suggested that long-acting ESA users were more resistant to ESA than short-acting ESA users by origin, and this difference may bias the study conclusion. Detailed information regarding patient characteristics for the first to the third tertiles of long-acting and short-acting ESA users may help better understanding. As review team members in the Pharmaceuticals and Medical Devices Agency, the authority for new drug approval in Japan, we consider the study as a preliminary analysis at this moment, and more careful interpretation and further well designed, randomized, controlled trials are necessary to draw a solid conclusion. Of note, no significant difference for mortality was observed in a recent meta-analysis of randomized, controlled trials comparing DA and EPO.4 Disclosures None.
Estrogen receptor alpha positive breast cancer patients with high levels of promoter C driven ESR1 transcripts show non-favorable prognosis
Authors: Sandra Amaral, Werner Schroth, Peter Fritz, Hiltrud Brauch
Journal: Cancer Research (2008)

978  At the time of diagnosis about 75% of breast cancers show positive estrogen receptor alpha (ERα) protein expression and this information currently guides the decision in favor of endocrine therapy. Tamoxifen treatment succeeded to control the disease in nearly 50% of ERα-positive cases but the non-responder sub-population needs further attention. There is a possibility that different ESR1 transcripts driven by promoter A and C influence ERα expression and may play a role in tamoxifen response. Formalin-fixed paraffin-embedded tissue samples of 138 patients diagnosed with breast cancer between 1988 and 1999 were retrieved from the RBK Pathology Department, Stuttgart, Germany. ERα-status was established by immunohistochemistry, RNA was extracted from punched tumor areas, and transcript levels of ESR1-C (promoter C driven)and ESR1-ex3 (contributed by all promoters) were quantified by QPCR. mRNA stability of ESR1-C, ESR1-A (promoter A driven), and ESR1-ex3 transcripts was measured in Actinomycin D treated ER-positive MCF-7 cells. Kaplan Meier survival analysis was used to analyze the relationship between levels of ESR1 expression and recurrence or breast cancer related death. Patients with ERα-positive tumors and over-expression of ESR1-C had a significant decrease of overall survival (OR=5.24 95%CI 1.06-25.96). In Cox regression analysis using stage, tumor size, nodal status, grading as covariates ESR1-C expression showed to be an independent prognostic factor of overall survival (HR=2.29 95% CI 1.06-4.94). With respect to ESR1 mRNA stability ESR1-C showed longer half-life when compared to ESR1-A and ESR1-ex3, i.e. 7.4, 2.8 and 5.3 hours, respectively (ANOVA p