tbuckley/cabot-search huggingface dataset:
A comparative analysis of prophylactic antimicrobial use in long-term care facilities in Ireland, 2013 and 2016
Authors: Meera Tandan, Rory O’Connor, Karen Burns, Helen Murphy, Sarah Hennessy, Fiona Roche, Sheila Donlon, Martin Cormican, Akke Vellinga
Journal: Eurosurveillance (2019)

Background Long-term care facilities (LTCFs) are important locations of antimicrobial consumption. Of particular concern is inappropriate prescribing of prophylactic antimicrobials. Aim We aimed to explore factors related to antimicrobial prophylaxis in LTCFs in Ireland. Methods The point prevalence surveys of Healthcare-Associated Infections in Long-Term Care Facilities (HALT) were performed in Ireland in May 2013 and 2016. Data were collected on facility (type and stewardship initiatives) and resident characteristics (age, sex, antimicrobial and indication) for those meeting the surveillance definition for a HAI and/or prescribed an antimicrobial. Results In 2013, 9,318 residents (in 190 LTCFs) and in 2016, 10,044 residents (in 224 LTCFs) were included. Of the 10% of residents prescribed antimicrobials, 40% were on prophylaxis, most of which was to prevent urinary tract infection. The main prophylactic agents were: nitrofurantoin (39%) and trimethoprim (41%) for urinary tract (UT); macrolides (47%) for respiratory tract and macrolides and tetracycline (56%) for skin or wounds. More than 50% of the prophylaxis was prescribed in intellectual disability facilities and around 40% in nursing homes. Prophylaxis was recorded more often for females, residents living in LTCFs for more than 1 year and residents with a urinary catheter. No difference in prophylactic prescribing was observed when comparing LTCFs participating and not participating in both years. Conclusions Forty per cent of antimicrobial prescriptions in Irish LTCFs were prophylactic. This practice is not consistent with national antimicrobial prescribing guidelines. Addressing inappropriate prophylaxis prescribing in Irish LTCFs should be a key objective of antimicrobial stewardship initiatives.
Lnc‐UCID Promotes G1/S Transition and Hepatoma Growth by Preventing DHX9‐Mediated CDK6 Down‐regulation
Authors: Yun‐Long Wang, Jin‐Yu Liu, Jin‐E Yang, Xiao‐Man Yu, Zhan‐Li Chen, Ya‐Jing Chen, Ming Kuang, Ying Zhu, Shi‐Mei Zhuang
Journal: Hepatology (2019)

Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a limited number of them have been functionally characterized. Here, we identified an oncogenic lncRNA, named lnc‐UCID ( lnc RNA u p‐regulating C DK6 by i nteracting with D HX9). Lnc‐UCID was up‐regulated in hepatocellular carcinoma (HCC), and a higher lnc‐UCID level was correlated with shorter recurrence‐free survival of HCC patients. Both gain‐of‐function and loss‐of function studies revealed that lnc‐UCID enhanced cyclin‐dependent kinase 6 (CDK6) expression and thereby promoted G1/S transition and cell proliferation. Studies from mouse xenograft models revealed that tumors derived from lnc‐UCID‐silenced HCC cells had a much smaller size than those from control cells, and intratumoral injection of lnc‐UCID small interfering RNA suppressed xenograft growth. Mechanistically, the 850‐1030‐nt domain of lnc‐UCID interacted physically with DEAH (Asp‐Glu‐Ala‐His) box helicase 9 (DHX9), an RNA helicase. On the other hand, DHX9 post‐transcriptionally suppressed CDK6 expression by binding to the 3′‐untranslated region (3′UTR) of CDK6 mRNA. Further investigation disclosed that lnc‐UCID enhanced CDK6 expression by competitively binding to DHX9 and sequestering DHX9 from CDK6‐3′UTR. In an attempt to explore the mechanisms responsible for lnc‐UCID up‐regulation in HCC, we found that the lnc‐UCID gene was frequently amplified in HCC. Furthermore, miR‐148a, whose down‐regulation was associated with an increase of lnc‐UCID in HCC, could bind lnc‐UCID and inhibit its expression. Conclusion : Up‐regulation of lnc‐UCID, which may result from amplification of its gene locus and down‐regulation of miR‐148a, can promote HCC growth by preventing the interaction of DHX9 with CDK6 and subsequently enhancing CDK6 expression. These findings provide insights into the biological functions of lncRNAs, the regulatory network of cell cycle control, and the mechanisms of HCC development, which may be exploited for anticancer therapy.
Abstract 17068: Ventricular Strain is Abnormal in Children With Hypertension
Authors: W R Thompson, Kathryn W Holmes, Jacky M Jennings, Tammy M Brady
Journal: Circulation (2013)

Background: Left ventricular hypertrophy (LVH) is an established marker of end- organ damage in children with hypertension. Abnormal diastolic function and peak systolic strain may precede the development of LVH in children with hypertension. Objective: To determine the association between LVH, diastolic function and peak systolic strain among children with hypertension. Methods: 50 hypertensive children aged 3-18 yrs were evaluated by echocardiography. LVH was considered present when left ventricular mass index [LVMI] by M-mode was >95th percentile. Left ventricular diastolic function parameters, including mitral valve inflow (E, A, deceleration time) and septal tissue Doppler (E’, A’), were assessed based on normal values for children. Global peak systolic strain, longitudinal and circumferential, was measured by 2D speckle tracking from apical 4-chamber and parasternal short axis views, respectively. Abnormal strain was defined as <5th percentile. Students t-tests and chi-squared analyses were used to ...
Navigating the landscape of core outcome set development in dermatology
Authors: Cecilia A.C. Prinsen, Phyllis I. Spuls, Jan Kottner, Kim S. Thomas, Christian Apfelbacher, Joanne R. Chalmers, Stefanie Deckert, Masutaka Furue, Louise Gerbens, Jamie Kirkham, Eric L. Simpson, Murad Alam, Katrin Balzer, Dimitri Beeckman, Viktoria Eleftheriadou, Khaled Ezzedine, Sophie E.R. Horbach, John R. Ingram, Alison M. Layton, Karsten Weller, Thomas Wild, Albert Wolkerstorfer, Hywel C. Williams, Jochen Schmitt
Journal: Journal of the American Academy of Dermatology (2019)
Five years of experience in patients with histopathological diagnosis of breast cancer.
Authors: Consuelo Hernandez Alvarez
Journal: Journal of Clinical Oncology (2015)

e12607 Background: Breast cancer is the leading cause of death in women in Mexico, and this is a heterogeneous disease, which requires a multidisciplinary approach. Objective: To assess the characteristics of the specimens with the diagnostic of breast cancer, obtained from the files of the Department of pathology of the Hospital Angeles Pedregal. Methods: We realize a retrospective, descriptive and longitudinal study from 417 histopathological reports with a diagnosis of breast cancer, during the period of January 2009 to December 2013 in Hospital Angeles Pedregal. Results: We obtained from the 417 cases that the main histopathological type was the ductal infiltrating carcinoma with 71.94%; the conservative surgical treatment was conducted in a 24.4% while radical surgery treatment was made in 36%. The results of immunohistochemistry were classified according to: estrogen receptor positive 83.64%, positive progesterone receptors 77.10%; HER-2 positive in 76 and negative in 248 specimens. The Mortality rate was 1.9% which results below the national average. Conclusions: These results are consistent with the criteria of diagnosis and treatment in our country. They assess the characteristics of the tumor, histological type and results of immunohistochemistry. It is essential to recognize that the morbidity of this pathology is duly detectable and close monitoring is essential to improve the quality of life of the patients.
Colonoscopy versus less invasive approaches for colorectal cancer (CRC) screening (Scr): A strategic perspective.
Authors: Afsaneh Barzi, Heinz-Josef Lenz, David I. Quinn, Sarmad Sadeghi
Journal: Journal of Clinical Oncology (2015)

6523 Background: Colonoscopy (CS) is an effective approach to Scr for CRC. Given its invasive nature, interest exists to find other Scr strategies (STs) with DNA stool testing being the most recent. Stool tests (STT) are dichotomous and a positive test typically results in a CS and then a negative CS would dictate the future Scr regime. We compared Scr STs in terms of their effectiveness (E), costs (C), and cost effectiveness (CE) to define the characteristics of a test or ST that can successfully compete or replace CS. Methods: Using a societal perspective, 12 STs and No Scr were compared. Using a Markov model 100,000 simulated individuals (SIs) 50 to 75 years of age with average risk of CRC were followed for up to 35 years. E (life years gained- LYG) and C (C of Scr and CRC) were calculated per SI. Results: CS dominates all other STs and has the highest LYG and lowest C even compared to No Scr. Under various sensitivity analyses (SA) we find that the results remain stable, primarily due to the high sensitivity (Sen) and specificity (Spe) of CS. DNA testing is not competitive, even among STT, given its high C and minimal improvement on E. For DNA to be competitive compared to other STT, its C must decrease or its Sen must improve. Conclusions: CS remains the unrivaled Scr test for CRC. Given CS’s impact on incidence by detecting and eliminating precancerous polyps, dichotomous stool testing strategies are at a disadvantage. Value proposition for a new Scr ST is in a departure from dichotomous reporting and providing risk levels that can identify precancerous polyps and influence the Scr regime after a negative CS. This should be regarded as the focus of Scr research and development. ST LYG Costs ICER No Scr 14.12 $3,511 # FO 14.12 $3,419 # FIT 14.12 $3,523 # FO+ FS 14.13 $3,322 # FIT+FS 14.13 $3,409 # CS 14.14 $3,186 0 FS 14.14 $3,591 # FO @2 14.12 $3,493 # FIT @2 14.12 $3,551 # FO @2+FS 14.13 $3,445 # FIT @2+FS 14.13 $3,496 # DNA 14.12 $5,439 # DNA @3 14.12 $4,315 # Abbreviations: FO: Fecal Occult Blood Testing, FIT: Fecal Immunochemical Test, FS: Flexible Sigmoidoscopy, @2: at 2 year intervals, @3: at 3 year intervals. Sen for test: FO 64%, FIT: 82%, FS: 75%, CS 95%, DNA 92%. Spe in SA for all tests was 90%. ICER: Incremental Cost Effectiveness Ratio. #: Absolute Dominance.
The Lung Microbiota In Stable Adult Asthma Differs According To Inflammatory Phenotype, Sex, And Atopy
Authors: G. B. Rogers, L. E. Leong, P. G. Gibson, I. A. Yang, S. J. Hodge, P. N. Reynolds, A. L. James, J. W. Upham, C. Jenkins, M. Peters, M. Baraket, J. L. Simpsons
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Inactivation of highly potent regulatory T cells (Tregs) with TNFR2 antagonist antibodies as a novel cancer immunotherapy approach.
Authors: Denise L. Faustman
Journal: Journal of Clinical Oncology (2015)

e14020 Background: Regulatory T cells (Tregs) are considered a barrier to cancer immunotherapy success due to their suppression of antitumor immune responses. Both murine and human data support the development of a Treg inhibition approach to enhance various oncology treatments. In particular, therapies that eliminate TNFR2hi Tregs, which are highly abundant in human tumors, show favorable clinical responses. The restricted tissue distribution of human TNFR2, with very high TNFR2 expression, make this cell surface target highly desirable. Recent ovarian and AML human tumor data verifies the potency of TNFR2-expressing Tregs in vivo. TNFR2 also determines Treg fate: in vitro blockage in murine models prevents Treg development. Therefore, TNFR2 antagonism may be an effective, targeted way to inhibit Tregs and boost cancer immunotherapy efficacy. Methods: Monoclonal antibodies (moAbs) against human TNFR2 were produced using a hybridoma line and screened on fresh human CD4+ T cells from > 500 healthy human subjects. MoAb functional capacity and mechanism of action were assessed in in vitro human assays by incubating expanded human Tregs with moAb candidates. Inhibition of TNFR2 transcript signaling was one readout to verify identification of TNFR2 antagonistic antibodies. Results: Several moAbs were identified as TNFR2 antagonists that suppressed the baseline or induced CD4 proliferation. After incubation with human Tregs for 24 hrs, TNFR2 antagonists turned off NFkB signaling in Tregs, rapidly inhibiting proliferation and resulting in selective Treg death. Important transcription factors such as TRAF2, IL2R and Foxp3 were downregulated. Remaining Tregs appeared unaltered in surface markers but showed low TNFR2 expression. Conclusions: Select anti-TNFR2 moAbs can be identified to this receptor and safely inactivate human TNFR2hi Tregs. Antibody antagonism through TNFR2 may be a targeted method to deplete and inactivate these potent Tregs, providing a novel way to enhance the efficacy of cancer immunotherapies.
Benefit of fluoropyrimidine based adjuvant chemotherapy in rectal cancer according to its pathological response: Results from an observational study.
Authors: MaryTere Herrera, German Caderillo-Ruiz, Dr. Consuelo Diaz, Erika B. Ruiz Garcia, Connie Zuratzi Deneken, Abraham Ruiz
Journal: Journal of Clinical Oncology (2015)

e14694 Background: In patients with locally advanced rectal cancer, neoadjuvant chemoradiotherapy remains as the standard approach; however, there is uncertainty as to the benefit of postoperative chemotherapy. The aim of the present analysis is to determine whether patients can benefit from adjuvant treatment. Methods: Observational study. Patients with rectal adenocarcinoma completed neoadjuvant chemoradiotherapy and then received adjuvant treatment according to their pathological response for a total of 6 months. Patients with a complete pathological response (ypT0N0) and with ypT1-4N0 received fluoropyrimidine-based chemotherapy (weekly 5FU 500mg/m2 with leucovorin 20 mg/m2 over two hours day 1) or Capecitabine (1250mg/m2 twice daily, days 1 to 14 every 3 weeks); finally, patients with stage III disease (ypT1-4N1-2) received modified FOLFOX6 (Oxaliplatin 85 mg/m2 every 2 weeks in combination with Fluorouracil 400 mg/m2 bolus day 1 with folinic acid 400 mg/m2 over two hours, followed by 2400 mg/m2 over 46 hours) or CapeOx (Capecitabine 100 mg/m2 twice daily days 1 to 14 with oxaliplatin 130 mg/m2 day 1). The primary endpoints were overall survival and disease free survival. Results: Between January 2005 and September 2012, 134 patients with stage II/III rectal cancer were enrolled in the database. Of these, 49 patients refused chemotherapy due mainly to economic issues and were offered active surveillance. A total of 85 patients received adjuvant chemotherapy, 19 (22%) had a ypT0N0, 25 (48%) had a ypT1-4N0 and 25 (29%) had a ypT1-4N1-2. Four patients (2.9%) had disease progression during the adjuvant treatment. Median overall survival in the chemotherapy group was 23.3 months ( 95% IC, 4.5-137.5 months) versus 8.2 months in the control group (CI 95%, 4.9 – 19.8 months), p < 0.05. Disease free survival in the chemotherapy group was 125.1 months (CI 95%, 2- 128.14 months) versus 60 months of the control group (95% IC, 1.2-76 months), p < 0.05. Conclusions: Adjuvant chemotherapy significantly prolonged overall and disease free survival. Rectal cancer patients may benefit from this approach according to the response to neoadjuvant treatment.
Proposal for tripartite re-classification of T1 renal cell carcinoma into cT1a (very low risk), cT1b (low risk), and cT1c (intermediate risk) substages.
Authors: Aaron Bradshaw, Robert Uzzo, Alessandro Larcher, Ahmed Eldefrawy, Umberto Capitanio, Shreyas Joshi, Stephen Ryan, Margaret Frances Meagher, Brittney Cotta, Addison Yee, Fang Wan, Francesco Montorsi, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2019)

618 Background: Criteria for staging of T1 renal tumors into T1a (≤4cm) and T1b (4cm&lt; and ≤7cm) have remained unchanged since 1997. Advancements in tumor biology have noted the heterogeneous potential of T1 renal tumors. We hypothesized that a three-tier classification may more rationally risk stratify T1 renal masses than the current T1a/T1b system. Methods: Multicenter (UCSD, Fox Chase Cancer Center, Ospadele San Raffaele) retrospective analysis of patients with cT1 renal cell carcinoma treated between 1987 and 2018. Patients were stratified into three groups: cT1a (≤2cm, very low risk), cT1b (2cm&lt; and ≤5cm, low risk), and cT1c (5cm&lt; and ≤7cm, intermediate risk). Primary outcome was recurrence free survival (RFS). Secondary outcome was overall survival (OS). Multivariable Cox Regression analysis (MVA) and Kaplan-Meier analyses (KMA) were utilized. Results: 3,324 patients were stratified into proposed T1 groups (T1a=578, T1b=2111, T1c=635; median follow-up 50 months). For cT1a, cT1b and cT1c, KMA revealed 5 year RFS of 96.9%, 91.6%, and 80.6% (p&lt;0.001), and 5 year OS of 91.9%, 86.3%, and 76.2% (p&lt;0.001). MVA for RFS revealed increasing age (HR=1.02, p&lt;0.001), diabetes mellitus (HR=1.36, p=0.04), high tumor grade (HR=2.22, p&lt;0.001) and tumor stage (Referent T1a; cT1b HR=2.18 p=0.001, cT1c HR=5.01 p&lt;0.001) as independent risk factors. MVA for OS revealed increasing age (HR=1.05, p&lt;0.001), diabetes mellitus (HR=1.57, p&lt;0.001), high tumor grade (HR=1.34, p=0.002) and tumor stage (Referent T1a; cT1b HR=1.26 p=0.1, cT1c HR=2.050 p&lt;0.001) as risk factors. Conclusions: Subclassification of cT1 renal cell carcinoma into three clinical stage categories corresponds to distinctive tumor groups whose biological potential varies significantly. Division into three distinct categories may enhance risk stratification, refine preoperative counseling, and augment postoperative follow-up protocols by delineating a very low risk and intermediate risk subset of renal tumors. [Table: see text]
A prospective study to evaluate the usefulness of the clanging tuning fork test and the nerve conduction velocity test for oxaliplatin-induced peripheral neuropathy.
Authors: Yoshinori Hirashima, Takuya Hanaoka, Koichiro Watanabe, Kengo Nagashina, Takashi Inagaki, Kazuo Nishikawa, Yasushi Hisamatsu, Ryotaro Morinaga, Satoshi Otsu, Toshihide Kumamoto, Kuniaki Shirao
Journal: Journal of Clinical Oncology (2015)

544 Background: Neurotoxicity is the most frequent dose-limiting toxicity of oxaliplatin. Cumulative sensory peripheral neurotoxicity results in discontinuation of chemotherapy for cancer and impairs neurological function irreversibly. To develop new strategies to continue chemotherapy according to the treatment plan without more severe neurotoxicity, objective assessment tools for oxaliplatin-induced peripheral neuropathy (OIPN) are needed. The clanging tuning fork test (CTFT) and the nerve conduction velocity test (NCVT) are widely used forbenign neuropathies. However, little is known about their clinical usefulness for OIPN. Methods: Colorectal cancer patients were prospectively monitored at baseline and during chemotherapy with modified FOLFOX6. The incidence and severity of OIPN were recorded using NCI-CTC grading (ver. 4.0). CTFT was conducted every 2 weeks and NCVT every 8 weeks. A generalized estimating equation model was used to examine the correlations between NCI-CTC grade and CTFT/NCVT. The accuracy of the assessment was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Twenty-one patients without peripheral sensory neuropathy (PSN) were enrolled. Mean CTFT values were 13.4 ± 0.7 sec at baseline, 14.1 ± 0.4 sec with grade 0 PSN, 14.0 ± 0.4 sec with grade 1 PSN, 12.5 ± 0.7 sec with grade 2 PSN, and 7.5 ± 0.9 sec with grade 3 PSN. The mean CTFT value with grade 3 PSN was significantly shorter than with the other grades (p&lt;.001, all). ROC curve analysis showed that variation in CTFT provides a high-accuracy assessment of grade 3 PSN (AUC=0.898, 95% CI: 0.764-1.000, p=.004), and its optimal cut-off value was -3.5 sec (sensitivity and specificity for grade 3 PSN were 86% and 79%, respectively). Unlike CTFT, NCVT showed little association with OIPN. Conclusions: CTFT was found to be very effective for assessing grade 3 OIPN. The present results suggest that CTFT, a simple, quick, and non-invasive examination, is a promising assessment tool for OIPN. Clinical trial information: 000004305.
A Longitudinal Toxicity over Time (ToxT) Analysis of Bortezomib When Added to Bendamustine-Rituximab (BR) in Previously Untreated High Risk (HR) Follicular Lymphoma (FL) from in E2408
Authors: Fangxin Hong, Andrew M. Evens, Paul J Novotny, Thomas M. Habermann, Ranjana H Advani, Randy D. Gascoyne, Thomas E. Witzig, Andrew Quon, Erik A. Ranheim, Amylou C. Dueck, Brad S Kahl, Gita Thanarajasingam
Journal: Blood (2018)
Comparison of clear cell ovarian cancer in Asian versus Caucasians: A NRG/GOG study.
Authors: Katherine Cynthia Fuh, James Java, Daniel Stuart Kapp, Robert Allen Burger, Robert C. Young, David Samuel Alberts, William P. McGuire, Maurie Markman, John K. Chan
Journal: Journal of Clinical Oncology (2015)

e16572 Background: Previous studies have shown that clear cell ovarian cancer is associated with a poor survival. In this current study, we propose to determine the differences in the presentation and outcomes in clear cell carcinomas for Asians versus Caucasians. Methods: Patients enrolled in NRG/GOG studies for ovarian cancer (GOG 95, 104, 111, 114, 157, 158, 172, 175, 182, and 218) were included in this analysis. Pearson chi-square test and Wilcoxon-Mann-Whitney, and Cox proportional hazards model were used. All statistical tests were two-tailed, with the significance level set at p=0.05. Results: Of 7,914 patients enrolled in epithelial ovarian cancer GOG trials from 1986-2009, 6.5%(516 patients) had clear cell carcinomas. 43(16%) of Asian patients had clear cell compared to 473 (6%) of Caucasians. 31 (72.1%) Asians with clear cell histology presented at a younger age of 53.7 (47.7-59.5) years compared to the 300 (63.4%) Caucasians who presented at 55 (48.2-62.7) years of age. 28 (65.2%) Asians had early stage disease compared to 251 (53.0%) of Caucasians (p=0.234). Of those with advanced stage disease, optimal cytoreduction to no gross residual disease was achieved in 9 (60.0%) of the Asians compared to 137 (61.7%) of Caucasians with clear cell tumors. The 5-year DSS of Asians with early stage disease (Stage I and II) versus Caucasians was 85.2% and 86.6%, respectively (p=0.655); the 5-year DSS of Asians with advanced stage clear cell (Stage III and IV) cancer versus Caucasians was 14.4% and 28.9% (P=0.128). On multivariate analysis, clear cell histology in Asians portended for a poor survival (HR 1.67, 95% CI: 1.01-2.76; p=0.046) compared to clear cell carcinoma in Caucasians after adjusting for other covariates include age, stage, and surgery. Conclusions: Compared to Caucasians, Asians with clear cell ovarian cancer presented at younger age, earlier stage, and had poor survival, particularly in those with advanced disease. Treatment and management of advanced stage clear cell cancers between Asians and Caucasians should be further evaluated.
Upregulation alpha 2 beta 1 and alpha 4 beta 1 on first trimester hemopoietic and mesenchymal stem cells mediates adhesion to laminin and fibronectin: A mechanism for homing to fetal liver and bone marrow.
Authors: J de la Fuente, K O'Donoghue, J Chan, S Kumar, N M Fisk, Roberts Iag.
Journal: Blood (2003)