tbuckley/cabot-search huggingface dataset:
Hollow microneedle-mediated micro-injections of a liposomal HPV E743–63 synthetic long peptide vaccine for efficient induction of cytotoxic and T-helper responses
Authors: Koen van der Maaden, Jeroen Heuts, Marcel Camps, Maria Pontier, Anton Terwisscha van Scheltinga, Wim Jiskoot, Ferry Ossendorp, Joke Bouwstra
Journal: Journal of Controlled Release (2017)

Recent studies have shown that intradermal vaccination has great potential for T cell-mediated cancer immunotherapy. However, classical intradermal immunization with a hypodermic needle and syringe has several drawbacks. Therefore, in the present study a digitally controlled hollow microneedle injection system (DC-hMN-iSystem) with an ultra-low dead volume was developed to perform micro-injections (0.25-10μL) into skin in an automated manner. A synthetic long peptide derived from human papilloma virus formulated in cationic liposomes, which was used as a therapeutic cancer vaccine, was administered intradermally by using the DC-hMN-iSystem. Fused silica hollow microneedles with an inner diameter of 50μm and a bevel length of 66±26μm were successfully fabricated via hydrofluoric acid etching. Upon piercing these microneedles into the skin using a protrusion length of 400μm, microneedles were inserted at a depth of 350±55μm. Micro-injections of 1-10μL had an accuracy between 97 and 113% with a relative standard deviation (RSD) of 9%, and lower volumes (0.25 and 0.5μL) had an accuracy of 86-103% with a RSD of 29% in ex vivo human skin. Intradermal administration of the therapeutic cancer vaccine via micro-injections induced strong functional cytotoxic and T-helper responses in mice, while requiring much lower volumes as compared to classical intradermal immunization. In conclusion, by using the newly developed DC-hMN-iSystem, very low vaccine volumes can be precisely injected into skin in an automated manner. Thereby, this system shows potential for minimally-invasive and potentially pain-free therapeutic cancer vaccination.
Abstract 12995: Prevalence and Incidence of Atrial Fibrillation in a Population Implanted With Cardiac Resynchronization Therapy Devices Implanted for at Least 30 Days: Evidence From a Prospective Clinical Trial
Authors: David L Hayes, Joao V Monteiro, Ruth Klepfer, Nathan A Grenz, Stelios I Tsintzos, Simon Eggington, Bimal R Shah
Journal: Circulation (2016)

Introduction: Atrial Fibrillation (AF) is an important contributor to insufficient left ventricular pacing and mortality in patients undergoing cardiac resynchronization therapy (CRT). The incidence and prevalence of AF post-CRT implant, in patients with and without previous history of AF, has not previously been described. Hypothesis: AF prevalence in CRT patients, despite history of AF, is higher than previously understood. Methods: Subjects implanted with a CRT-Defibrillator (CRT-D) enrolled in the PainFree SST study and with device data collection were analyzed. Subjects who exited within 30 days of implant, had &lt; 27 days of available daily AT/AF burden data, or had ≥ 10% of daily AT/AF data missing were excluded. We defined incidence and prevalence of clinically meaningful device documented AF using previously published criteria (≥1 day with AF &gt; 6 hours). History of AF at enrollment was documented based on clinical history. Results: The analysis included 944 patients (68±11 years; 78% male, EF 28±9%, QRS 152±29 ms; 59% NYHA III/IV). The duration from implant to study exit or death was 2.0 ± 0.8 years (IQR 1.5-2.5). History of AT/AF was documented in 37% of patients at baseline. Overall, any AT/AF was found in 85.2 % of subjects during follow-up. Clinically meaningful AT/AF was found in 30.3% of subjects. Of the 345 subjects with history of AF at baseline, 51.9% had clinically meaningful AT/AF during follow-up vs.17.9% for subjects without known AF (p&lt;0.0001). 24.8% of subjects experienced at least one day of ≥ 23h of AT/AF. 6.9% of subjects had ≥ 23h of AT/AF for &gt; 95% of days with data. Conclusions: AF occurs in a substantial proportion of CRT-D patients and clinically documented history of AF prior to CRT-D implant corresponds poorly with device documented AT/AF during follow-up. Device documented AF should be evaluated in CRT-D patients with and without previous history of AF to individualize strategies to maximize left ventricular pacing and minimize disruption due to AF.
Abstract 18071: Whole Body Periodic Acceleration Prevents Cardiac Ischemic-Reperfusion Injury by Transcriptional Regulation of Diverse Cytoprotective Signaling Pathways
Authors: Francis X McGowan, Deborah J Watson, Arkady Uryash, Malley Thomas O, Huamei He, Viany M Nadkarni, Robert A Berg, Jose A Adams
Journal: Circulation (2016)

Background: Periodic acceleration (pGz) delivers sinusoidal inertial forces (~0.3 x g) along the spinal (z) axis which imparts modest increases in pulsatile shear stress. pGz improves functional re...
Effect of creative writing on mood in cancer patients.
Authors: Muhammad Azam Hussain, Junjia Zhu, Joseph Drabick, Aditya Joshi, Erika Saunders, Cristina I. Truica, Michael Hayes, Monika Joshi
Journal: Journal of Clinical Oncology (2017)

178 Background: Patients with cancer may have significant mental health comorbidity. Creative writing has a substantial history in providing a wide range of psychological benefits for cancer patients. Methods: We conducted a pilot study to determine feasibility whether cancer patients can be enrolled, randomized and retained for four weeks for creative writing classes (Feasibility was defined as 50% of our enrolled patients on intervention arm (IA) could attend at least 2 classes). We anticipated enrolling 45 patients over the period of 2 months with randomization into 2 arms: IA and standard of care (SOC). “Write from the Heart”, a series of creative writing workshops (CWW) were conducted on IA. Subjects in IA had four, 2-hour weekly CWW whereas SOC arm did not receive any sessions. We used validated Emotional Thermometer Scales (ETS), ranging from 0 (best)-10 (worst), to predict changes in parameters reflecting patient’s mental health pre and post intervention. ETS has five dimensions (distress, anxiety, depression, anger and need help), which are all continuous variables. Results: Total of 16 patients were accrued -11 in IA and 5 in SOC. 7 out of 11 (63%) patients enrolled in IA attended at least 75% of classes. Comparisons were made using two-sample T-tests. Although sample size was small, analysis showed intriguing results. IA did show a decreasing pattern on Total Emotion Score (TES). For each visit, post-class scores were lower than pre-class scores. SOC versus IA and IA intragroup analysis (Paired T-test) did not reveal any statistical significance. Conclusions: We observed that it is feasible for cancer patients to attend focused workshops geared towards mental health wellbeing. Although not statistically significant, IA showed trend towards mood improvement. A second study is planned with a single arm for all cancer patients. In addition to using emotional thermometers, we will include questionnaires to evaluate mental health symptoms effectively. Further prospective clinical studies should be conducted to evaluate effect of this intervention in cancer patients. Clinical trial information: Study 00006541. [Table: see text]
Host modulation therapy with anti‐inflammatory agents
Authors: Philip M. Preshaw
Journal: Periodontology 2000 (2017)

Abstract Host modulation therapy refers to a treatment concept in which drug therapies are used as an adjunct to conventional periodontal treatment to ameliorate destructive aspects of the host inflammatory response. This strategy is not new in the treatment of periodontitis. Previously, nonsteroidal anti‐inflammatory drugs have been investigated in this regard, with evidence of reductions in alveolar bone resorption when these drugs are used for prolonged periods of time. However, the risk of significant unwanted effects precludes the use of both nonselective nonsteroidal anti‐inflammatory drugs and the selective cyclooxygenase‐2 inhibitors as adjunctive treatments for periodontitis. Currently, the only available adjunctive host response modulator that is licensed for the treatment of periodontitis is subantimicrobial dose doxycycline, which functions as an inhibitor of matrix metalloproteinases. Although clinical benefits have been shown in carefully conducted randomized controlled trials, the efficacy of subantimicrobial dose doxycycline in routine clinical practice has yet to be determined. Anti‐cytokine therapies have been developed for use in the treatment of rheumatoid arthritis, the pathogenesis of which bears many similarities to that of periodontitis; however, the significant risk of unwanted effects (as well as cost and lack of human trials in the treatment of periodontal diseases) precludes the use of any of the currently available anti‐cytokine therapies in the treatment of periodontitis. The identification of pro‐resolving lipid mediators as well as small molecule biologicals that influence inflammatory responses offers the best potential, at the present time, for the development of novel host response modulators in periodontal therapy, but much research remains to be done to confirm safety and efficacy.
Polypharmacy and out-of-pocket medication costs in the last month of life among commercially insured patients with advanced cancer: Insights from linking a regional cancer registry and insurance claims.
Authors: Cara L. McDermott, Catherine R. Fedorenko, Mikael Anne Greenwood-Hickman, Karma L. Kreizenbeck, Ted Conklin, Bruce Smith, J. Randall Curtis, Gary H. Lyman, Scott David Ramsey
Journal: Journal of Clinical Oncology (2017)

79 Background: Polypharmacy, defined as the concurrent use of multiple medications, may expose patients to drug-drug interactions and excessive medication costs. Patients with advanced cancer may benefit from medication discontinuation when faced with life-limiting illness. While polypharmacy prevalence has been explored in older patients, there are limited data for younger patients with advanced malignancy. To better understand medication use in this population, we characterized medication use and associated out-of-pocket (OOP) costs in the last month of life among commercially insured subjects under age 65 who did not enroll in hospice. Methods: We linked enrollment and claims records from two regional commercial insurers to Surveillance, Epidemiology, and End Results (SEER) Cancer Surveillance System and Washington State Cancer Registry records for patients diagnosed with a stage IV solid tumor malignancy in Washington state between January 1, 2007-December 31, 2016. We excluded patients who did not incur at least 1 claim in their last month. We calculated OOP costs as the difference between allowed and paid claim amounts, adjusted to 2016 dollars. Results: See Table. Among 369 patients, the average age was 56 years (range 23-64) and 51% (n=189) were male. Patients most frequently had lung (n=149, 40%), pancreatic (n=36, 10%) or colorectal cancer (n=32, 9%). Patients had an average of 7 medication claims (range 1-26) in the last month of life; the most commonly observed non-chemotherapy claims were for opioids, benzodiazepines and anti-emetics. Conclusions: A majority of subjects incurred at least 5 medication claims in their last 30 days; almost one-third had 10 or more. Frequent claims were for medication for pain or other symptoms. OOP costs ranged considerably. Future research will focus on developing interventions to assure effective medication use congruent with patient and family preferences and goals of care. [Table: see text]
Phase III study of palonosetron (PALO) given as 30-min IV infusion (IV inf) versus 30-sec IV bolus (IV bol) for prevention of chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy (HEC).
Authors: Meinolf Karthaus, Péter Szabò, Daniel Voisin, Giada Rizzi, Tudor Ciuleanu
Journal: Journal of Clinical Oncology (2017)

227 Background: PALO (0.50 mg), a distinctive second-generation 5-HT 3 receptor antagonist (RA), is a component of the oral fixed combination agent NEPA, the second component being the NK 1 RA netupitant. Oral NEPA is approved for acute and delayed CINV prophylaxis after moderately (MEC) and HEC. This study was conducted in support of the NEPA IV formulation (0.25 mg PALO + 235 mg fosnetupitant) administered as a 30-min IV inf, currently under FDA review. Methods: Chemotherapy-naive patients (pts) with solid tumors were randomized (1:1) to receive a single 0.25-mg PALO as a 30-min IV inf or a 30-sec IV bol, 30 min before reference HEC (cisplatin; dacarbazine), with oral dexamethasone (20 mg [D1]; 8 mg BID [D2–4]) (NCT02557035). Primary objective: noninferiority (NI; lower limit of the 99% CI to be &gt; –15% [prespecified NI margin]) in complete response (CR; no emesis/no rescue) in the acute (0–24 h) phase. Secondary objective: safety. Results: 440 pts (median age 59.4 y [25–79]; cisplatin: 97.3%; dacarbazine: 2.7%) were randomized to IV inf (n=225) or IV bol (n=215). Baseline characteristics were similar. Acute CR rate was 82.7% (IV inf) and 86.5% (IV bol), with risk difference of –3.8% (99% CI: –12.2; 4.7) meeting the primary objective of NI. Treatment-emergent AE and study drug-related AE frequency was similar in both arms (Table). One PALO IV inf patient with pre-existing cardiac symptoms, experienced 1 serious AE that eventually lead to death and was considered possibly study drug-related by the investigator. No G≥3 infusion site reactions occurred. No patient in IV inf arm had infusion interruptions. Conclusions: PALO IV inf was noninferior to IV bol in acute CINV prevention after receiving non-AC HEC. Safety profiles were similar. No specific infusion toxicities were observed. The results show that PALO 0.25 mg IV inf is appropriate for the NEPA IV formulation. Clinical trial information: NCT02557035. [Table: see text]
Weekly nab-paclitaxel in elderly patients with classic Kaposi sarcoma.
Authors: Francesco Iuliano, Gian Luca Cervo, Eleonora Iuliano, Alessia Perricelli, Maria Luci, Angelo Pomillo, maria Aquila Santoro, Francesco Pontieri
Journal: Journal of Clinical Oncology (2016)

e22539 Background: Kaposi's sarcoma (KS) is a potentially life-threatening multifocal neoplasm that may represent a difficult therapeutic challenge in disseminated stages. Liposomal anthracyclines, or combination chemotherapy are widely used to treat this kind of patients.. The efficacy of taxanes (paclitaxel and docetaxel), as agents with antiangiogenic properties,has been described previously in the treatment of KS patients but the length of the infusion, the need for pre-medication with steroids and toxicity caused by solvents can limit their utilization , especially in elderly patients. Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication which can make it easier to tolerate .At the moment there are no studies on its efficacy and safety in older KS patients . Methods: After written informed consent was obtained a phase II trial was conducted with nab-paclitaxel in 6 patients with advanced-stage KS to assess its safety and antitumor activity. The mean age of patients was 74,8 years ( range 71-83). Nab-paclitaxel was administered at a fixed dose of 100 mg intravenously over 30 minutes administered weekly on days 1, 8, and 15 of each 4-week cycle for 4 cycles. No premedication to prevent hypersensitivity reactions was required before administration. Thereafter, if the patient experienced stable disease or better response, treatment doses were given every two weeks until complete disease remission, disease progression, or unacceptable toxicity occurred. Results: All patients improved dramatically after chemotherapy. Partial desinfiltration (n = 2) or complete desinfiltration (n = 4) of all papulonodular skin lesions was observed with marked improvement of lymphedema in 1 patient. Grade 3 neutropenia and thrombocytopenia were observed in three of six and one of six patients, respectively. It was not observed any grade 4 toxicity Conclusions: Classic KS predominantly affects elderly people over 60 years, many of whom do not tolerate aggressive chemotherapy regimens well due to frequent comorbidity and diminished cardiovascular and bone marrow reserves. Nab-paclitaxel has a good and rapid efficacy in our experience which involved a setting of patients difficult to manage.
Collectin-11 Promotes the Development of Renal Tubulointerstitial Fibrosis
Authors: Weiju Wu, Chengfei Liu, Conrad A. Farrar, Liang Ma, Xia Dong, Steven H. Sacks, Ke Li, Wuding Zhou
Journal: Journal of the American Society of Nephrology (2017)

Collectin-11 is a recently described soluble C-type lectin, a pattern recognition molecule of the innate immune system that has distinct roles in host defense, embryonic development, and acute inflammation. However, little is known regarding the role of collectin-11 in tissue fibrosis. Here, we investigated collectin-11 in the context of renal ischemia-reperfusion injury. Compared with wild-type littermate controls, Collec11 deficient (CL-11-/- ) mice had significantly reduced renal functional impairment, tubular injury, renal leukocyte infiltration, renal tissue inflammation/fibrogenesis, and collagen deposition in the kidneys after renal ischemia-reperfusion injury. In vitro, recombinant collectin-11 potently promoted leukocyte migration and renal fibroblast proliferation in a carbohydrate-dependent manner. Additionally, compared with wild-type kidney grafts, CL-11-/-mice kidney grafts displayed significantly reduced tubular injury and collagen deposition after syngeneic kidney transplant. Our findings demonstrate a pathogenic role for collectin-11 in the development of tubulointerstitial fibrosis and suggest that local collectin-11 promotes this fibrosis through effects on leukocyte chemotaxis and renal fibroblast proliferation. This insight into the pathogenesis of tubulointerstitial fibrosis may have implications for CKD mediated by other causes as well.
Development of a Function-Blocking Antibody Against Fibulin-3 as a Targeted Reagent for Glioblastoma
Authors: Mohan S. Nandhu, Prajna Behera, Vivek Bhaskaran, Sharon L. Longo, Lina M. Barrera-Arenas, Sadhak Sengupta, Diego J. Rodriguez-Gil, E. Antonio Chiocca, Mariano S. Viapiano
Journal: Clinical Cancer Research (2017)

Purpose: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NFκB signaling.Experimental Design: We used deletion constructs to identify a key signaling motif of fibulin-3. An mAb (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3. mAb428.2 was tested in cultures to measure its inhibitory effect on fibulin-3 signaling. Nude mice carrying subcutaneous and intracranial GBM xenografts were treated with the maximum achievable dose of mAb428.2 to measure target engagement and antitumor efficacy.Results: We identified a critical 23-amino acid sequence of fibulin-3 that activates its signaling mechanisms. mAb428.2 binds to that epitope with nanomolar affinity and blocks the ability of fibulin-3 to activate ADAM17, Notch, and NFκB signaling in GBM cells. mAb428.2 treatment of subcutaneous GBM xenografts inhibited fibulin-3, increased tumor cell apoptosis, and enhanced the infiltration of inflammatory macrophages. The antibody reduced tumor growth and extended survival of mice carrying GBMs as well as other fibulin-3-expressing tumors. Locally infused mAb428.2 showed efficacy against intracranial GBMs, increasing tumor apoptosis and reducing tumor invasion and vascularization, which are enhanced by fibulin-3.Conclusions: To our knowledge, this is the first rationally developed, function-blocking antibody against an ECM target in GBM. Our results offer a proof of principle for using "anti-ECM" strategies toward more efficient targeted therapies for malignant glioma. Clin Cancer Res; 24(4); 821-33. ©2017 AACR.
Laparoscopic and endoscopic cooperative surgery for difficult resection of posterior esophagogastric junction gastrointestinal stromal tumors
Authors: Jean-Michel Gonzalez, Antoine Debourdeau, Guillaume Philouze, Laura Beyer, Stéphane Berdah, Marc Barthet
Journal: Endoscopy (2017)

The esophagogastric junction (EGJ) is a rare location for gastrointestinal stromal tumors (GIST) and resection remains challenging in posterior/fundic lesions [1]. Laparoscopic and endoscopic cooperative surgery (LECS) is a new combined minimally invasive method [2] [3] [4]. Recently, a large series of 126 patients who underwent LECS for gastric submucosal tumors (86 GISTs) was published showing a high rate of feasibility and less than 5 % morbidity [5]. We report our experience in difficult gastric GIST resections.
Relative state, social comparison reactions, and the behavioral constellation of deprivation
Authors: Dallas Novakowski, Sandeep Mishra
Journal: Behavioral and Brain Sciences (2017)

Abstract Pepper &amp; Nettle compellingly synthesize evidence indicating that temporal discounting is a functional, adaptive response to deprivation. In this commentary, we underscore the importance of the psychology of relative state, which is an index of relative competitive (dis)advantage. We then highlight two proximate emotional social comparison reactions linked with relative state – personal relative deprivation and envy – that may play an important role in the deprivation-discounting link.
Phase III study of trifluridine/tipiracil versus placebo in Asian patients with metastatic colorectal cancer (TERRA study): Country subgroup
Authors: V. Sriuranpong, T.W. Kim, L. Shen, J. Xu, H. Pan, R. Xu, S. Han, T. Liu, Y.S. Park, C. Shi, Y. Bai, F. Bi, J.B. Ahn, S. Qin, Q. Li, C. Wu, F. Zhou, D. Ma, V. Srimuninnimit, J. Li
Journal: Annals of Oncology (2017)
Editorial board of public health journal quits after row with publisher
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The entire editorial board of the International Journal of Occupational and Environmental Health ( Int J Occup Environ Health ) have resigned following an acrimonious battle with the journal’s publisher Taylor & Francis.

The board said it was resigning in protest at the appointment of a new editor with links to industry without consulting the board and what it described as the “unilateral” withdrawal of approved articles.

The mass resignation was announced in a letter1 dated 22 November sent to Ian Bannerman, managing director at Taylor & Francis journals, from board member Arthur Frank.

The letter, published …