tbuckley/cabot-search huggingface dataset:
Antioxidative study of Cerium Oxide nanoparticle functionalised PCL-Gelatin electrospun fibers for wound healing application
Authors: Hilal Ahmad Rather, Ria Thakore, Ragini Singh, Dhwani Jhala, Sanjay Singh, Rajesh Vasita
Journal: Bioactive Materials (2017)

Skin wound healing involves a coordinated cellular response to achieve complete reepithelialisation. Elevated levels of reactive oxygen species (ROS) in the wound environment often pose a hindrance in wound healing resulting in impaired wound healing process. Cerium oxide nanoparticles (CeNPs) have the ability to protect the cells from oxidative damage by actively scavenging the ROS. Furthermore, matrices like nanofibers have also been explored for enhancing wound healing. In the current study CeNP functionalised polycaprolactone (PCL)-gelatin nanofiber (PGNPNF) mesh was fabricated by electrospinning and evaluated for its antioxidative potential. Wide angle XRD analysis of randomly oriented nanofibers revealed ∼2.6 times reduced crystallinity than pristine PCL which aided in rapid degradation of nanofibers and release of CeNP. However, bioactive composite made between nanoparticles and PCL-gelatin maintained the fibrous morphology of PGNPNF upto 14 days. The PGNPNF mesh exhibited a superoxide dismutase (SOD) mimetic activity due to the incorporated CeNPs. The PGNPNF mesh enhanced proliferation of 3T3-L1 cells by ∼48% as confirmed by alamar blue assay and SEM micrographs of cells grown on the nanofibrous mesh. Furthermore, the PGNPNF mesh scavenged ROS, which was measured by relative DCF intensity and fluorescence microscopy; and subsequently increased the viability and proliferation of cells by three folds as it alleviated the oxidative stress. Overall, the results of this study suggest the potential of CeNP functionalised PCL-gelatin nanofibrous mesh for wound healing applications.
Safety and tolerability of chemotherapy (CT) containing high doses of methotrexate (HD-MTX) and cytarabine (Ara-C) in patients with primary central nervous system lymphoma (PCNSL) and hepatitis B virus (HBV) infection
Authors: T. Calimeri, P. Lopedote, M. Repetto, A. Vignati, M. Sassone, C. Cecchetti, S. Perrone, M. Foppoli, G. Ciboddo, S. Girlanda, J. Peccatori, A. Chiara, M. Memoli, A. Ferreri
Journal: Annals of Oncology (2017)

Background: HBV reactivation is a serious complication of some anticancer therapies. Preliminary studies suggested high rates of HBV reactivation, with fatal outcome, in pts with PCNSL treated with standard HD-MTX-based CT. Risk of HBV reactivation is further increased by the use of Rituximab (Rtx), which significantly improves efficacy of CT in PCNSL. Hence, HBV-positive pts are usually excluded from prospective trials, with a negative effect on accrual, and are treated with less intensive therapies, resulting in lower cure rates. Herein, we report the incidence of HBV infection and reactivation in a mono-institutional series of PCNSLs treated with modern strategies. Methods: HIV-negative pts with newly diagnosed PCNSL treated with CT containing HD-MTX and Ara-C ± rituximab at our Institution, from 2010 to 2016, were analyzed to establish incidence of HBV infection, hepatotoxicity and treatment-related viral reactivation. Results: 48 pts (median age 58, range 29–76) were considered. Eight (17%) pts had "resolved" HBV infection (negative HBsAg but positive anti-surface [anti-HBs] or anti-core [anti-HBc] Antibodies), one (2%) pt had active infection. HBV prophylaxis with lamivudine was indicated in 3/8 pts with resolved HBV. The pt with active infection was treated with entecavir. Induction comprised HD-MTX plus Ara-C in 2 pts, HD-MTX, Ara-C and Rtx in 2, and HD-MTX, Ara-C, thiotepa and Rtx in 5 (MATRix). Transient grade 1-2 elevation of hepatic enzymes (AST, ALT, GGT) was observed in all pts; grade 3-4 was recorded in 17/39 (44%) HBV-negative pts and in 5/9 (56%) HBV-positive pts (Fisher exact; p = 0.71). Eight out of 9 HBV-positive pts received the 4 planned CT courses without dose reductions due to hepatotoxicity; six pts achieved a CR and received consolidation (WBRT 2, ASCT 3, lenalidomide maintenance 1). At a median follow-up of 27 months for the whole series (12-88), no pt experienced HBV reactivation during first-line treatment, 5 pts remain relapse-free. Conclusions: This study suggests that MTX-Ara-C-based therapy, MATRix regimen, in particular, can be safely used in PCNSL pts with HBV infection, without impaired life expectancy. Legal entity responsible for the study: IRCCS San Raffaele Funding: None Disclosure: All authors have declared no conflicts of interest.
Abstract 15836: Assessment of High-risk Atherosclerotic Plaque by Dual-energy Coronary Computed Tomography in Sudden Cardiac Death Patients: Mapping With Histopathologic Gold Standard
Authors: Asim Rizvi, Fay Y Lin, Bríain Ó Hartaigh, Donghee Han, Ji Hyun Lee, Lohendran Baskaran, Kazuyuki Yahagi, Robert Kutys, David Fowler, James Earls, James K Min, Renu Virmani
Journal: Circulation (2016)

Introduction:  Necrotic core (NC) is a surrogate of high-risk plaque identified by histopathologic analysis in sudden coronary death (SCD) victims. Non-invasive discrimination of NC from fibrous plaque (FP) is challenging at present due to overlapping Hounsfield Units (HU) between NC and FP. Dual-energy CT (DECT) as a novel imaging technique, enables differentiation of tissue materials based upon atomic density and evaluation of images based on monochromatic energies (MCE) rather than polychromatic spectra of energies by single-energy CT (SECT).   Hypothesis:  To determine whether DECT could improve discrimination of high-risk plaque features, and compare DECT-MCE to SECT for discrimination of NC from FP.   Methods:  Coronary specimens were obtained from 12 post-mortem hearts from autopsy-validated SCD victims. NC and FP were identified on histologic sections. Histology images with a ≥90% uniform region of interest (ROIs) of NC and FP, and corresponding to a 0.4 mm 2  area, were created. HU values for SECT and DECT-MCE (ranging from 40 to 140 kilo-electron voltages [keV]) were calculated for histologic ROIs based on NC and FP. Standardized HU were defined as the mean HU measure divided by the corresponding lumen mean HU measure for NC and FP. The maximum difference in standardized median HU values between NC and FP were then calculated at each DECT-MCE to determine the optimal viewing mode for diagnosis of NC.   Results:  Of 136 sections, a total 56 ROIs (23 NCs and 33 FPs) were measured. Across a range of DECT-MCE, varying minimum differences in standardized median HU values between NC and FP was displayed, with the highest difference at 140 keV (0.25, NC 0.12, FP 0.37) and lowest difference at 60 keV (0.10, NC: 0.37; FP: 0.47). Compared to DECT-MCE, SECT was poorer at discrimination of NC and FP, with a minimum difference of 0.07 between NC and FP.   Conclusions:  DECT is superior to SECT for discrimination of NC and FP in coronary lesions from SCD victims, with a 140 keV MCE performing best for DECT.
Summary of head-to-head comparisons of patient (pt) risk classifications by the 21-gene recurrence score (RS) assay and other genomic assays for early breast cancer (EBC)
Authors: Z. Varga, P. Sinn, D. McCullough, A. Lau, M.C. Stöppler, F.L. Baehner, C. Chao, A. Seidman
Journal: Annals of Oncology (2017)
Causal and Noncausal Processes Underlying Being Bullied
Authors: Judy Silberg, Kenneth S. Kendler
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Ixekizumab treatment for psoriasis: integrated efficacy analysis of three double-blinded, controlled studies (UNCOVER-1, UNCOVER-2, UNCOVER-3)
Authors: K.A. Papp, C.L. Leonardi, A. Blauvelt, K. Reich, N.J. Korman, M. Ohtsuki, C. Paul, S. Ball, G.S. Cameron, J. Erickson, L. Zhang, L. Mallbris, C.E.M. Griffiths
Journal: British Journal of Dermatology (2017)

Ixekizumab, a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A, is approved for the treatment of moderate‐to‐severe psoriasis. This analysis represents an overview of the efficacy outcomes from three phase III psoriasis studies. Data were integrated from the 12‐week induction period of three studies in which patients received ixekizumab 80 mg every 2 weeks (IXE Q2W; n =1169) or every 4 weeks (IXE Q4W; n =1165) after an initial 160‐mg dose for both; etanercept (50 mg biweekly; n =740; two studies) or placebo (n =792). The coprimary end points were the percentages of patients with response of static Physician's Global Assessment (sPGA; score 0 or 1) and ≥ 75% improvement in baseline Psoriasis Area and Severity Index (PASI 75) at week 12. Response rates were compared between treatments using the Cochran–Mantel–Haenszel test stratified by study. Treatment comparisons with placebo included data from three studies, whereas etanercept comparisons were based on two studies. Ixekizumab treatment was superior to placebo (P <0·001) and etanercept (P <0·001) on sPGA (0, 1) and PASI 75, with significant differences in PASI improvement at week 1. With IXE Q2W, at week 12, the frequencies of patients achieving PASI 75, 90 and 100 were nearly 90%, 70% and 40%, respectively. Ixekizumab‐treated patients showed significantly greater improvement vs. placebo and etanercept in percentage body surface area involvement and fingernail psoriasis. IXE Q2W was superior to IXE Q4W on all treatment outcomes. Ixekizumab therapy at both dosing regimens demonstrated rapid onset and superior efficacy to placebo and etanercept, with IXE Q2W providing better outcomes than IXE Q4W during the first 12 weeks of treatment.
NHS aims to expand emergency department workforce to combat pressures
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The NHS has unveiled plans to expand the emergency department workforce to tackle current pressures and ensure that the health service meets its “core priority” of improving emergency performance.

The blueprint,1 developed by the Royal College of Emergency Medicine, NHS England, NHS Improvement, and Health Education England, commits additional funding to help grow the clinical workforce, reduce attrition in medical training, and improve staff retention in emergency departments around England.

The investment in the existing and trainee clinical workforce will create “safe, sustainable staffing” in emergency departments by boosting numbers at consultant level and in the broader clinical workforce, the plan says.

Emergency medicine is already set to be the fastest growing specialty over …
J-FORCE study: A randomized, double-blind, placebo-controlled phase III study evaluating olanzapine (5 mg) combined with standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based, highly emetogenic chemotherapy
Authors: H. Hashimoto, S. Iwasa, M. Abe, T. Yanai, S. Zenda, T. Yamaguchi, H. Kaba, H. Fukuda, H. Terakado, Y. Ohe
Journal: Annals of Oncology (2017)
Oncotype DX score, menopausal status and body mass index
Authors: S. Picardo, J. Sui, M. Greally, B. Woulfe, L. Prior, L. Corrigan, C. O'Leary, W. Mullally, J. Walshe, J. McCaffrey, M. O'Connor, D. O'Mahony, L. Coate, R. Gupta, S. O'Reilly
Journal: Annals of Oncology (2017)
Inhibition of the MEK1/2/ERK1/2 pathway sensitizes human leukemia cells to perifosine-mediated lethality through a JNK-, Akt-, and Mcl-1-dependent process
Authors: Mohamed Rahmani, Paul Dent, Steven Grant
Journal: Cancer Research (2006)

1345  The alkyl-lysophospholipid (ALP) perifosine has been shown to activate the MEK1/2/ERK1/2 pathway in a variety of tumor cells including leukemia cells. However, the effects of blocking the MEK1/2/ERK1/2 pathway on the response of such cells to perifosine has not been examined. To address this issue, we exposed human leukemia (U937) and other malignant hematopoietic cells to various concentrations of perifosine in the presence or absence of the pharmacologic MEK1/2 inhibitors PD184352 and U0126 for 24 hrs, after which various indicators of mitochondrial injury, caspase activation, activation status of relevant signaling pathways, and apoptosis were monitored. Here we report that inhibition of MEK1/2/ERK1/2 pathway using PD184352 or U0126 strikingly enhances perifosine-mediated mitochondrial dysfunction and cell death in U937 cells. Such events were manifested by cytochrome c, AIF, and Smac/DIABLO release into the cytosol, caspase-3, -8, and -9 activation, apoptosis, and a marked decrease in cell growth. Similar effects were observed in HL-60 as well as in MM1S myeloma cells. These events were associated with disruption of multiple cell-survival signaling pathways including inactivation of ERK1/2 and Akt, and a pronounced activation of the stress-related p46 JNK pathway. They were also associated with a decrease in Mcl-1 protein levels, and a marked conformational change in Bax accompanied by its translocation to the membrane fraction. Enforced expression of constitutively active (myristoylated) Akt markedly reduced PD184352/perifosine-mediated cell death. In addition, molecular or pharmacological inhibition of JNK activation using siRNA against JNK1 or SP 600125 respectively, significantly attenuated PD184352/perifosine-induced apoptosis. Such findings suggest that Akt inactivation and JNK activation play important functional roles in the lethality mediated by these agents. Furthermore, ectopic expression of Mcl-1 protein strongly inhibited PD184352/perifosine-mediated apoptosis in U937 cells indicating a functional role for Mcl-1 downregulation in synergistic antileukemic interactions between these agents. Together, these findings support the notion that activation of the MEK1/2/ERK1/2 pathway plays a cytoprotective role in perifosine-mediated cell killing, and that inhibition of this pathway strikingly enhances perifosine-mediated mitochondrial injury and apoptosis. They also indicate that this process involves, at least in part, Akt inactivation, JNK activation, and Mcl-1 downregulation. Collectively, these observations raise the possibility that combining perifosine with agents that inhibit the MEK1/2/ERK1/2 pathway such as PD184352 or other clinically relevant MEK1/2 inhibitors may represent a novel strategy against leukemia and possibly other hematologic malignancies.
Multicenter randomized phase II study of chemoradiation (CRT) followed by surgery (S) and chemotherapy (CT) versus induction CT followed by CRT and S in high-risk rectal cancer: GCR-3 final efficacy and safety results
Authors: C. Fernandez-Martos, J. Aparicio, A. Salud, V. Alonso, B. Massuti, M. Safont, R. Vera, P. Escudero, J. Maurel, C. Pericay
Journal: Journal of Clinical Oncology (2009)

4103 Background: In locally advanced RC the optimal therapeutic sequence remains an important clinical question. Induction CT prior to CRT and S may be associated with better efficacy and compliance. Methods: Eligible pts had medium or distal high risk RC defined by MRI and/or US: Tumors within 2mm of mesorectal fascia, distal T3 at/below levators, resectable T4 and T3N+. Pts, stratified by center, were randomized assigned to receive either Arm A : capecitabine (Cap) 825 mg/m2 BID 5 d/w, oxaliplatin (Ox) 50 mg/m2 IV weekly x 5 and concomitant RT: 50.4 Gy in 28 fractions. S was planned 5–6 w after CRT. Post-op four cycles of Cap 1,000 mg/m2 bid days 1 to 14; Ox 130 mg/m2 day 1 or Arm B: Induction CapOx followed by CRT and S. Two parallel, Simon 2-stage designs: α=0.05 β=0.1; 24 evaluable pts/arm 1 st stage and 54 pts/arm for 2 nd stage. Primary endpoint: pathological complete response (pCR). Secondary endpoints included toxicity and treatment compliance. Results: 108 Pts were randomly assigned (arm A/B, 52/56), and 103 were assessable (49/54) from 14 sites. Median age 62/60 years, Male 65/70%. During treatment period 6 pts died A/B: 2 vascular, 1 suicide/ 3 post-op. Pts with any grade ¾ toxicity during CRT were arm A/B: 29% (14/49) and 23% (12/53). Any grade ¾ toxicity during adjuvant/induction CT were 51% (19/37) and 17% (9/54); χ 2 ,p= 0.0004. On an intent-to-treat basis the pCR for Arm A/B was achieved in seven (13.5%; 95% CI, 5.6%-25.8%) and eight (14.3%; 95% CI, 6.4%-26.2%). R0 resections were achieved in 92% (45/49) and 88% (48/54). 51% (25/49) and 93% (50/54) received all four cycles of adjuvant/induction CT (χ 2 ;p&lt;0.0001). Relative Median Dose intensity of adjuvant /induction CT was 0.74/0.96 (Wilcoxon; p&lt;0.0001) for Cap and 0.75/1.0 (Wilcoxon; p&lt;0.0001) for Ox. Conclusions: Induction CT prior to CRT has more favorable compliance and toxicity profiles. Furthermore, there is no compromise in pCR and R0 resection rates. Larger trials evaluating this strategy are justified. [Table: see text]
Short- and Long-term Prognosis of Patients With Acute Heart Failure With and Without Diabetes: Changes Over the Last Three Decades
Authors: Jan C. van den Berge, Alina A. Constantinescu, Hendrik J. Boiten, Ron T. van Domburg, Jaap W. Deckers, K. Martijn Akkerhuis
Journal: Diabetes Care (2017)

We studied differences in long-term (i.e., 10 year) prognosis among patients with acute heart failure (HF) with and without diabetes over the last three decades. In addition, we investigated whether the degree of prognostic improvement in that period was comparable between patients with and without diabetes.This prospective registry included all consecutive patients aged 18 years and older admitted to the Intensive Coronary Care Unit with acute HF in the period of 1985-2008. A total of 1,810 patients were included; 384 patients (21%) had diabetes. The outcome measure was the composite of all-cause mortality, heart transplantation, and left ventricular assist device implantation after 10-year follow-up.The 10-year outcome in patients with diabetes was significantly worse than in those without diabetes (87% vs. 76%; adjusted hazard ratio [HR] 1.17 [95% CI 1.02-1.33]). Patients admitted in the last decade had a significantly lower 10-year event rate than patients admitted in the first two decades, both among patients without diabetes (adjusted HR 0.86 [95% CI 0.75-0.99]) and patients with diabetes (adjusted HR 0.80 [95% CI 0.63-1.00]).The long-term outcome of patients with diabetes is worse than that of patients without diabetes. However, the long-term prognosis improved over time in both groups. Importantly, this improvement in long-term prognosis was comparable in patients with and without diabetes. Despite these promising results, more awareness for diabetes in patients with acute HF is necessary and there is still need for optimal treatment of diabetes in acute HF.
Phase 1 study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC)
Authors: M. Morris, N.J. Vogelzang, O. Sartor, A. Armour, M. Groaning, R. Messmann, A. Robarts, D.P. Petrylak, A. Tolcher, M.S. Gordon, H. Babiker
Journal: Annals of Oncology (2017)
GW28-e0071 The Effect of Mild Hypothermia on Neurons Autophagy after Cerebral Ischemia Reperfusion in Sirt1 Knockout Mice
Authors: Hongyan Wei, Chunlin Hu, Hengjie Li, Yan Yang, Yuanzheng Lu, Bo Li, Xiaoxing Liao
Journal: Journal of the American College of Cardiology (2017)
Split dosing of daratumumab (D) in a phase 1b study of D plus carfilzomib (K)-based regimens in patients (pts) with multiple myeloma (MM)
Authors: S.Z. Usmani, A. Jakubowiak, A. Chari, S. Lonial, M.-V. Mateos, L. Benboubker, K. Wu, N.Z. Khokhar, J. Wang, P. Doshi, P. Moreau
Journal: Annals of Oncology (2017)
Relationship between pretreatment levels of circulating DNA, circulating tumor cells, CEA, CA19.9 and tumor burden on CT scan in patients treated for a metastatic colorectal cancer
Authors: M. Hassine, C. Savoye-Collet, D. Sefrioui, L. Beaussire, A. Gillibert, A. Gangloff, N. Sarafan-Vasseur, P. Michel, F. Di Fiore
Journal: Annals of Oncology (2017)
Young-age onset colorectal cancer: Analysis of incidence, clinical features and outcomes
Authors: F.K. Fujiki, M.F.B. Vicentini, A.C.B. Silva, E.M. Zambrano, L.G. Fonseca, M.I. Braghiroli, J. Sabbaga, P.M. Hoff
Journal: Annals of Oncology (2017)
Capecitabine and temozolomide (CAPTEM) in neuroendocrine tumor of unknown primary.
Authors: Aman Chauhan, Arun Kumar Arumugam Raajasekar, Zin Myint, Leaundra Murray, Lowell Brian Anthony
Journal: Journal of Clinical Oncology (2017)

e15691 Background: Better diagnostics, recognition and knowledge of neuroendocrine tumors (NETs) have led to consistent growth in incidence and prevalence of the disease. Being an orphan disease, therapeutic options are limited. Scarce data exists regarding use of Capecitabine and Temozolomide (CAPTEM) in neuroendocrine tumors. There are no published data on use of CAPTEM in neuroendocrine tumors of unknown primary. NETs of unknown primary accounts for 10-15 % of NETs. Historically NETs with unknown primary are thought to be relatively aggressive, conferring a poorer prognosis. Methods: Patients with neuroendocrine tumor with unknown primary were identified from Markey Cancer Center database over a five-year period (2012-2016). Patients treated with CAPTEM regimen were analyzed for radiological response in first scan, time to progression on treatment and toxicity. IRB approval was obtained. Results: 56 patients with neuroendocrine tumors of unknown primary were identified. 12 patients were treated with CAPTEM. Median age of study cohort was 62 years. 6/12 were females. Seven patients were grade II, 4 were grade III and only one was grade I NET. CAPTEM was used as front line systemic therapy in 9 patients. Mean duration of treatment before progression was 10.8 months. 6 patients showed reduction in metastatic tumor volume at first q 3 monthly CT scan. 3 patients had stable disease and 3 patients showed disease progression at first surveillance scan. Following were the rates of common side-effects. Grade 2 thrombocytopenia (n = 4), Grade 1 lymphocytopenia (n = 3), hand/foot syndrome Grade 1 (n = 1), Grade 3(n = 1), Fatigue, Grade 1 (n = 6) Conclusions: CAPTEM shows activity in neuroendocrine tumor of unknown primary. Currently FDA approved treatment options for grade I and grade II GI NETs includes somatostatin analogs and everolimus. Both of which are cytostatic and of limited use in case of visceral crisis or bulky disease where disease shrinkage is required. CAPTEM should be considered for grade II NETS of unknown primary.
Combined radiofrequency ablation and ipilimumab in uveal melanoma: Results from the SECIRA-UM trial
Authors: E.A. Rozeman, W. Prevoo, M.A.J. Meier, K. Sikorska, B.A. van de Wiel, A. Broeks, H. van Tinteren, E. Kapiteijn, J.V. Thienen, J.B. Haanen, C.U. Blank
Journal: Annals of Oncology (2017)
Potential impact of avelumab+axitinib (A+Ax) on tumor size (TS) compared with historical data of sunitinib (S) as evaluated by a modeling and simulation (MS) approach
Authors: J. Zheng, A. Chang, J. Larkin, R.J. Motzer, M. Amantea, C. Bello, D. Pavlov, M. Geraldes, M. Martignoni, A. Di Pietro, G. Andrews
Journal: Annals of Oncology (2017)