tbuckley/cabot-search huggingface dataset:
Handheld Reflectance Confocal Microscopy for the Detection of Recurrent Extramammary Paget Disease
Authors: Oriol Yélamos, Brian P. Hibler, Miguel Cordova, Travis J. Hollmann, Kivanc Kose, Michael A. Marchetti, Patricia L. Myskowski, Melissa P. Pulitzer, Milind Rajadhyaksha, Anthony M. Rossi, Manu Jain
Journal: JAMA Dermatology (2017)

Extramammary Paget disease (EMPD) is commonly refractory to surgical and nonsurgical therapies. Identifying recurrent or persistent EMPD is challenging because the disease is multifocal, and multiple blind scouting biopsies are usually performed in this setting. Handheld reflectance confocal microscopy (HRCM) has been used to diagnose and map primary EMPD and therefore may be used to identify EMPD recurrences.To evaluate HRCM's diagnostic accuracy in the setting of recurrent or persistent EMPD as well as its potential diagnostic pitfalls.This prospective case series study included patients referred to the Dermatology Service at Memorial Sloan Kettering Cancer Center between January 1, 2014, and December 31, 2016, with biopsy-proven EMPD in whom HRCM was used to monitor treatment response. Five patients were included, and 22 sites clinically concerning for recurrent or persistent disease were evaluated using HRCM and histopathologic examination. In 2 patients, video mosaics were created to evaluate large areas.Sensitivity and specificity of HRCM in identifying recurrent or persistent EMPD; causes for false-negative results according to their location, histopathologic findings, and previous treatments.Of the 22 clinically suspicious sites evaluated in 5 patients (4 men, 1 woman; median [range] age, 70 [56-77] years), 9 (40.9%) were positive for recurrent disease on HRCM and histopathologically confirmed, and 13 (59.1%) sites were negative on HRCM, but 3 of the 13 were positive for EMPD on histopathological examination. In general, HRCM had a sensitivity of 75% and a specificity of 100% in identifying recurrent or persistent EMPD. False-negative results were found in 2 patients and occurred at the margins of EMPD, close to previous biopsy sites. Creating video mosaics (or video mosaicking) seemed to improve the detection of EMPD.Handheld reflectance confocal microscopy is a useful auxiliary tool for diagnosing EMPD recurrences and can be used to guide scouting biopsies, thus reducing the number of biopsies needed to render a correct diagnosis.
Randomized controlled trial of cash incentives or peer mentors to improve HCV linkage and treatment among HIV/HCV coinfected persons who inject drugs: the CHAMPS Study
Authors: M. Sulkowski, K. Ward, O. Falade-Nwulia, J. Moon, C. Sutcliffe, S. Brinkley, T. Haselhuhn, D. Thomas, S. Katz, K. Herne, L. Arteaga, S. Mehta
Journal: Journal of Hepatology (2017)
Notes from the Field: Severe Human Metapneumovirus Infections — North Dakota, 2016
Authors: Claire M. Midgley, Jill K. Baber, Holly M. Biggs, Twila Singh, Michelle Feist, Tracy K. Miller, Kirby Kruger, Susan I. Gerber, John T. Watson, Molly A. Howell
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

On May 27, 2016, CDC was informed by North Dakota Department of Health of a recent cluster of severe respiratory illnesses that included two deaths in children at a large hospital (hospital A) in Fargo, North Dakota, caused by human metapneumovirus (HMPV).An investigation was initiated to explore possible risk factors for illness.HMPV is a cause of both upper and lower respiratory tract infections, including bronchiolitis and pneumonia, particularly among young children (1) and older adults (2).In the United States, the typical HMPV season extends from November-February through May-July (3).No vaccine is currently available to prevent HMPV infection.Six HMPV-positive pediatric inpatients (median age = 2.5 years) were identified at hospital A during April-May 2016.Diagnostic tests were performed at a commercial laboratory using a reverse transcription-polymerase chain reaction (RT-PCR)-based respiratory virus panel (RVP).The number of HMPV infections detected and the percentage of HMPV-positive respiratory virus panels from hospital A did not appear high compared with the same period in 2015 (hospital A, unpublished data, 2015 and 2016).Among the six patients identified in 2016 (Table ), five had underlying medical conditions, including premature birth (three), congenital heart disease (three), bronchopulmonary dysplasia (two), developmental delay (three), and cerebral palsy (two).Four children required mechanical ventilation, and two of the four had acute respiratory distress syndrome and pneumothorax.Two of the six patients died; both had considerable medical comorbidities.Four of the patients were American Indian; all four survived, although two required mechanical ventilation and two required supplemental oxygen.Two of the four American Indian children were transferred to hospital A from an Indian Health Service facility.During preliminary discussions with the North Dakota Department of Health, local
Hesperetin conjugated PEGylated gold nanoparticles exploring the potential role in anti-inflammation and anti-proliferation during diethylnitrosamine-induced hepatocarcinogenesis in rats
Authors: Gokuladhas Krishnan, Jayakumar Subramaniyan, Pramila Chengalvarayan Subramani, Barath Muralidharan, Devaki Thiruvengadam
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Liver cancer is the fifth most common cancer and one of the leading causes of death in the world, and second most common cause of death in men. Natural products emerge as the most enduring approaches in the development of anticancer targeting drug. Hesperetin (HP), one of the abundant flavonoids found naturally in citrus fruits, has received considerable attention in anti-cancer promotion and progression. The present study was conducted to decipher the role of 0.5 ml hesperetin conjugated gold nanoparticles (Au-mPEG(5000)-S-HP NPs) during diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male Wistar albino rats and shows the better antioxidant that possesses anti-inflammatory, anti-proliferation and anticarcinogenic properties and may modulate signaling pathways. The confirmation of polymer functionalized gold nanoparticles and drug loaded polymer gold nanoparticles were characterized by HR-TEM with EDAX, and DLS with Zeta potential techniques. The drug encapsulation efficiency and release properties were carried out in PBS at pH 7.4 for Au- mPEG(5000)-S-HP and compared with the control pure hesperetin (HP). Here, we review the role of mast cell counts, tumor necrosis factor alpha (TNF-α), transcription factor nuclear factor-κB (NF-κB), levels of glycoconjugates, proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizing regions, are the master regulator of inflammation and proliferation, in the development of hepatocellular injury, liver fibrosis and HCC. DEN-administered animals showed increased mast cell counts, tumor necrosis factor alpha, transcription factor nuclear factor-κB, glycoconjugates, proliferating cell nuclear antigen, and argyrophilic nucleolar organizing regions. Whereas Au-mPEG(5000)-S-HP NPs supplementation considerably suppressed all the above abnormalities. These results suggest that the Au-mPEG(5000)-S-HP NPs exhibited the better potential anticancer activity by inhibiting cell inflammation and proliferation in DEN-induced hepatocellular carcinogenesis.
Written reminders increase vaccine coverage in Danish children - evaluation of a nationwide intervention using The Danish Vaccination Register, 2014 to 2015
Authors: Camilla Hiul Suppli, Mette Rasmussen, Palle Valentiner-Branth, Kåre Mølbak, Tyra Grove Krause
Journal: Eurosurveillance (2017)

We evaluated a national intervention of sending written reminders to parents of children lacking childhood vaccinations, using the Danish Vaccination Register (DDV). The intervention cohort included the full birth cohort of 124,189 children born in Denmark who reached the age of 2 and 6.5 years from 15 May 2014 to 14 May 2015. The reference cohort comprised 124,427 children who reached the age of 2 and 6.5 years from 15 May 2013 to 14 May 2014. Vaccination coverage was higher in the intervention cohort at 2.5 and 7 years of age. The differences were most pronounced for the second dose of the measles-mumps-rubella vaccine (MMR2) and the diphtheria-tetanus-pertussis-polio vaccine DTaP-IPV4 among the 7-year-olds, with 5.0 percentage points (95% confidence interval (CI): 4.5–5.4) and 6.4 percentage points (95% CI: 6.0–6.9), respectively. Among the 2.5 and 7-year-olds, the proportion of vaccinations in the preceding 6 months was 46% and three times higher, respectively, in the intervention cohort than the reference cohort. This study indicates a marked effect of personalised written reminders, highest for the vaccines given later in the schedule in the older cohort. In addition, the reminders increased awareness about correct registration of vaccinations in DDV.
A validation/evaluation of five postoperative prognostic tools for prostate cancer
Authors: B. A. Inman, B. C. Leibovich, S. A. Siddiqui, I. Frank
Journal: Journal of Clinical Oncology (2007)

5117 Background: Prognostic nomograms, scoring tools, and risk tables are rapidly accumulating in the prostate cancer (PCa) literature. It is not always clear to whom these tools should apply and how well they predict the outcomes they were designed to forecast. There is need for independent evaluation of these tools. Methods: We used the Mayo Clinic Radical Prostatectomy Registry, a prospective database of radical prostatectomy (RP) outcomes, to assess tools designed to predict RP outcomes. The validation set included 13,313 RP patients from 1990–2005. There were 3,256 PSA failures, 566 metastases, and 1,599 deaths (301 were due to PCa). We assessed the discrimination, calibration and overall accuracy of prediction tools identified through a structured Pubmed search. Results: Tools varied greatly in terms of complexity, width of prediction interval, and method of presentation. Several tools included non-standard variables and were therefore unevaluable, despite an extensive dataset, leaving the 1999 and 2005 Kattan nomograms, the 1998 and 2001 CDPR scores, and the 2001 GPSM score for analysis. Discrimination (quantitated by the c index) was better for PCa-specific survival and metastases than for PSA failure ( Table ). Kaplan-Meier plots demonstrated clustering of risk groups in most tools, most severely in the higher risk groups of the Kattan nomograms. The calibration plots of most tools (excepting GPSM) had a serious discordance between observed and predicted outcomes in the lower probability ranges. This meant that most tools gravely overestimated the probability of RP failure in high-risk patients, by up to 4- fold. Conclusions: The tools showed moderate discriminatory ability for PSA failure but performed much better for non-surrogate outcomes. Most tools (excepting GPSM) were miscalibrated in high risk patients and dramatically underestimated the efficacy of surgery in this cohort. Prognostic tools may not be as accurate as previously reported. [Table: see text] No significant financial relationships to disclose.
Protective effect of melatonin on carbon tetrachloride-induced chronic hepatotoxicity
Authors: N.P. Marroni, S.R. Bona, A.J. Moreira, G. Rodrigues, J. Noda, M.D.C. Soares, F.C. Di Naso, T.R. Da Silveira, C.A. Marroni
Journal: Journal of Hepatology (2017)
Exercise and other non-pharmaceutical interventions for cancer-related fatigue in patients during or after cancer treatment: a systematic review incorporating an indirect-comparisons meta-analysis
Authors: Roger Hilfiker, Andre Meichtry, Manuela Eicher, Lina Nilsson Balfe, Ruud H Knols, Martin L Verra, Jan Taeymans
Journal: British Journal of Sports Medicine (2017)

Aim To assess the relative effects of different types of exercise and other non-pharmaceutical interventions on cancer-related fatigue (CRF) in patients during and after cancer treatment. Design Systematic review and indirect-comparisons meta-analysis. Data sources Articles were searched in PubMed, Cochrane CENTRAL and published meta-analyses. Eligibility criteria for selecting studies Randomised studies published up to January 2017 evaluating different types of exercise or other non-pharmaceutical interventions to reduce CRF in any cancer type during or after treatment. Study appraisal and synthesis Risk of bias assessment with PEDro criteria and random effects Bayesian network meta-analysis. Results We included 245 studies. Comparing the treatments with usual care during cancer treatment, relaxation exercise was the highest ranked intervention with a standardisedmean difference (SMD) of −0.77 (95% Credible Interval (CrI) −1.22 to −0.31), while massage (−0.78; −1.55 to −0.01), cognitive–behavioural therapy combined with physical activity (combined CBT, −0.72; −1.34 to −0.09), combined aerobic and resistance training (−0.67; −1.01 to −0.34), resistance training (−0.53; −1.02 to −0.03), aerobic (−0.53; −0.80 to −0.26) and yoga (−0.51; −1.01 to 0.00) all had moderate-to-large SMDs. After cancer treatment, yoga showed the highest effect (−0.68; −0.93 to −0.43). Combined aerobic and resistance training (−0.50; −0.66 to −0.34), combined CBT (−0.45; −0.70 to −0.21), Tai-Chi (−0.45; −0.84 to −0.06), CBT (−0.42; −0.58 to −0.25), resistance training (−0.35; −0.62 to −0.08) and aerobic (−0.33; −0.51 to −0.16) showed all small-to-moderate SMDs. Conclusions Patients can choose among different effective types of exercise and non-pharmaceutical interventions to reduce CRF.
Siebzehn Jahre Strahlentherapie Der Krebse Zürcher Erfahrungen 1919–1935. [SEVENTEEN YEARS OF RADIATION THERAPY FOR CANCER. Cases from Zurich, 1919–1935.] Hans R. Schinz and Adolph Zuppinger. Leipzig: George Thieme, 1937, x + 340 pages. 95 illustrations and 213 tables. (Published and distributed by authority of the Alien Property Custodian, 1944.) Price $11.75
Authors: Maurice Lenz
Journal: Cancer Research (1946)
Long-term safety and efficacy of darbepoetin alfa in subjects with stage IV NSCLC receiving multi-cycle chemotherapy
Authors: P. Gascón, R. Nagarkar, M. Šmakal, K. Syrigos, C.H. Barrios, J. Cárdenas Sánchez, L. Zhang, D. Henry, D. Tomita, C. De Oliveira Brandao
Journal: Annals of Oncology (2017)
Selinexor and Low Dose Dexamethasone (Sd) in Patients with Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib and Anti-CD38 Ab Refractory Multiple Myeloma (MM): STORM Study
Authors: Dan T. Vogl, David Dingli, R. Frank Cornell, Carol Ann Huff, Sundar Jagannath, Divaya Bhutani, Rachid Baz, Ajay K Nooka, Joshua Richter, Craig E. Cole, Ravi Vij, Andrzej Jakubowiak, Rafat Abonour, Gary J. Schiller, Terri L. Parker, Luciano J. Costa, David Kaminetzky, James Hoffman, Andrew J. Yee, Ajai Chari, David S. Siegel, Rafael Fonseca, Scott VanWier, Gregory Ahmann, Ilsel Lopez, Michael Kauffman, Sharon Shacham, Jean-Richard Saint-Martin, Carla Picklesimer, Sharon Friedlander, Cassandra Choe-Juliak, A. Keith Stewart
Journal: Blood (2016)
The addition of splenic and superior mesenteric vein respiratory excursions to Baveno VI criteria can save more endoscopies without compromising its diagnostic accuracy
Authors: P. Del Poggio, D. Di Mauro, M. Buonocore, E. Oggionni, F. Ganz, S. Villa, M. Belotti, A. D’Alessio
Journal: Journal of Hepatology (2017)
Phase II study of FOLFOXIRI plus panitumumab (pmab) followed by evaluation for resection, in patients (pts) with metastatic KRAS wild-type colorectal cancer (mCRC) with liver metastases only.
Authors: Ahmed Zakari, Victor G. Gian, Anthony Alan Meluch, James D. Peyton, David Michael Waterhouse, Andrew J. Lipman, Ralph V. Boccia, Suzanne Fields Jones, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2014)

e14552 Background: Pts with liver-only mCRC who are not candidates for potentially curative resection may be converted to resectable with more aggressive chemotherapy regimens with higher response rates (RR). FOLFOXIRI has shown a higher RR and pts sent to resection than FOLFIRI. EGFR inhibitors improve RR by approximately 10%. This phase II, non-randomized, multicenter trial evaluated the RR of the combination of FOLFOXIRI plus pmab as first-line treatment for pts with KRAS wild-type mCRC with liver-only metastasis. Methods: Pts with liver-only KRAS wild-type mCRC received FOLFOXIRI (5-FU 3200 mg/m2 48-hour continuous IV; LV 200 mg/m2 IV; irinotecan 125 mg/m2 IV; oxaliplatin 85 mg/m2 IV) and pmab (6 mg/kg IV) day 1 of each 14-day cycle. Restaging occurred every 4 cycles. Surgical evaluation occurred at baseline and with each restaging. The primary endpoint was overall RR. Secondary endpoints included: rate of R0 resection, progression-free survival (PFS), overall survival (OS), and safety. Results: Fifteen pts were enrolled: median age 55 yrs, 87% male, 8 pts (15%) were resectable at baseline. Pts received a median of 6 cycles (1 – 33). Common treatment-related grade 3 toxicities included diarrhea (33%), and rash (20%). One pt (7%) experienced grade 4 neutropenia. Of the 12 pts evaluable for clinical response, 9 pts achieved partial response (PR), and stable disease was noted in 3 pts. RR of evaluable pts was 75%. Nine pts continued to resection all of which were pPR; 8 (88%) had R0 resection. Median PFS was 13.3 months (95% CI: 4.2 – NA). Median OS is not yet reached. As the trial enrolled new data emerged of expanded KRAS/NRAS mutations and potential for negative interaction with oxaliplatin-based therapy. For this reason the trial was halted and pts on study underwent expanded KRAS/NRAS mutation analysis. 6/15 pts have had analysis performed. None of the tested pts were found to have additional KRAS/NRAS mutation. Conclusions: FOLFOXIRI-pmab is a well-tolerated regimen with high RR. This study was stopped early due to the necessity of expanded KRAS/NRAS testing, but this regimen is a viable option for the treatment of pts with liver-only mCRC. Clinical trial information: NCT01226719.
Inhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myeloma
Authors: Salomon Manier, Daisy Huynh, Yu J. Shen, Jia Zhou, Timur Yusufzai, Karma Z. Salem, Richard Y. Ebright, Jiantao Shi, Jihye Park, Siobhan V. Glavey, William G. Devine, Chia-Jen Liu, Xavier Leleu, Bruno Quesnel, Catherine Roche-Lestienne, John K. Snyder, Lauren E. Brown, Nathanael Gray, James Bradner, Luke Whitesell, John A. Porco, Irene M. Ghobrial
Journal: Science Translational Medicine (2017)

Targeting translation initiation in multiple myeloma induces inhibition of a specific oncogenic translation program.
Dasatinib and rapamycin synergistically inhibit the proliferation of cells expressing oncogenic KIT kinase via global inhibition of AKT-dependent signaling
Authors: Marcus Schittenhelm, Alida Theil, Sharon Shiraga, Francis Lee, Michael Heinrich
Journal: Cancer Research (2007)

5416  Activating mutations of KIT are found in association with several human neoplasms including subsets of patients with GIST, AML or systemic mast cell disorders (SM). Tyrosine kinase inhibitors have proven clinical activity in these diseases, but responses are largely partial or incomplete. We previously demonstrated that dasatinib (formerly BMS-354825), a small-molecule low ATP-competitive inhibitor of SRC and ABL tyrosine kinases, potently inhibits imatinib-sensitive as well as -resistant mutant KIT isoforms. We now show that, inhibition of KIT phosphorylation (as a surrogate for kinase activation) does not completely inhibit AKT activity allowing continued activation of the mTOR-p70S6kinase pathway. In our study, we used mastocytosis, leukemia and hematopoietic cell lines with endogenous or exogenous mutant KIT isoforms (wildtype, D816V, D816Y, V560G). The inhibitory effect of dasatinib and/or rapamycin on KIT-dependent downstream pathways was evaluated by immunoblotting. In addition, the antiproliferative and pro-apoptotic effects of monotherapy vs. combination therapy were also evaluated. We report herein, that KIT activates downstream pathways important for cell viability and cell survival including the MAP Kinase (MAPK), STAT and PI3K/AKT pathways. Dasatinib inhibited KIT activation and resulted in decreased phosphorylation of members of the MAPK1/2, STAT3 and AKT pathways. Notably, dasatinib treatment abolished phosphorylation of AKT Ser-473 whereas AKT Thr-308 remained constitutively phosphorylated. This partial inhibition of AKT activity was insufficient to completely inhibit downstream kinases, such as p70S6Kinase, a known substrate of mTOR (Target Of Rapamycin). To determine the biological effect of more completely inhibiting AKT-dependent signaling, we tested combinations of dasatinib with rapamycin, using doses of that did not have any significant anti-tumor effects when administered as monotherapy. The combination of dasatinib and rapamycin demonstrated strong additive to synergistic inhibition of cellular proliferation and induction of apoptosis. We conclude that inhibition of oncogenic KIT signaling by dasatinib is insufficient to completely inhibit AKT-dependent signaling (e.g. p70S6kinase). Thus, combination therapy of KIT-dependent malignancies using a TKI such as dasatinib along with rapamycin may improve clinical efficacy compared with TKI monotherapy.
Viral Dominance patterns in hepatitis delta patients are associated with distinct systemic inflammatory patterns which influence response to interferon therapy
Authors: G.L. Lutterkort, W. Anika, J. Hengst, C. Yurdaydin, K. Weber, S. Hardtke, O. Keskin, M. Manns, H. Wedemeyer, B. Heidrich
Journal: Journal of Hepatology (2017)