tbuckley/cabot-search huggingface dataset:
Abstract 14201: Angiogenic Effects of Local Sustained Release of MicroRNA-126 in Murine Hindlimb Ischemia
Authors: Shinichi Tsumaru, Kenji Minakata, Hidetoshi Masumoto, Koh Ono, Masayasu Izuhara, Kazuhiro Yamazaki, Tadashi Ikeda, Ryuzo Sakata
Journal: Circulation (2016)

Introduction:  Recent studies demonstrate that microRNAs hold a promising potential in therapeutic intervention including angiogenesis. microRNA-126 (miR-126) is reported to regulate angiogenesis by blocking Sprouty-related protein 1 (SPRED-1), an endogenous inhibitor of vascular endothelial growth factor (VEGF) signaling pathway. In this study, we investigated angiogenic effects of local sustained release of miR-126 loaded with poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) in a murine hindlimb ischemia model.   Methods:  We induced mice unilateral hindlimb ischemia by left femoral artery resection. We randomly assigned the mice in 2 groups and performed intramuscular injection of miR-126-loaded PLGA-NPs or scrambled miR-loaded PLGA-NPs just after induction of ischemia.   Results:  miR-126 expression levels in ischemic limb at 3 days after treatment were significantly higher in mice treated with miR-126-loaded PLGA-NPs compared to those with scrambled miR, indicating fair efficiency of local miR transduction (P   Conclusion:  miR-126 increased neovascularization, and thus improved tissue perfusion in a murine hindlimb ischemia. The present study suggests that local sustained release of miR-126-loaded PLGA-NPs might be an effective method in therapeutic angiogenesis for limb ischemia.
Case report of de Clerembault syndrome, bipolar affective disorder, and response to lithium
Authors: G Remington, H Book
Journal: American Journal of Psychiatry (1984)

De Clerembault identified a syndrome associated with delusional loving, and it has since been described in association with various diagnoses including paranoia, schizophrenia, affective disorder, and mental retardation. The authors document its coexistence with bipolar disorder and its response to lithium.
The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh
Authors: Anisha Solanki, Ching-In Lau, José Ignacio Saldaña, Susan Ross, Tessa Crompton
Journal: The Journal of Experimental Medicine (2017)

Before birth, B cells develop in the fetal liver (FL). In this study, we show that Gli3 activity in the FL stroma is required for B cell development. In the Gli3-deficient FL, B cell development was reduced at multiple stages, whereas the Sonic hedgehog (Hh [Shh])-deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hh-reporter mouse showed that Shh signals directly to developing B cells and that Hh pathway activation was increased in developing B cells from Gli3-deficient FLs. RNA sequencing confirmed that Hh-mediated transcription is increased in B-lineage cells from Gli3-deficient FL and showed that these cells expressed reduced levels of B-lineage transcription factors and B cell receptor (BCR)/pre-BCR-signaling genes. Expression of the master regulators of B cell development Ebf1 and Pax5 was reduced in developing B cells from Gli3-deficient FL but increased in Shh-deficient FL, and in vitro Shh treatment or neutralization reduced or increased their expression, respectively.
Association of Previous Clinical Breast Examination With Reduced Delays and Earlier-Stage Breast Cancer Diagnosis Among Women in Peru
Authors: Anya Romanoff, Tara Hayes Constant, Kay M. Johnson, Manuel Cedano Guadiamos, Ana María Burga Vega, Joseph Zunt, Benjamin O. Anderson
Journal: JAMA Oncology (2017)

Mammographic screening is impractical in most of the world where breast cancers are first identified based on clinical signs and symptoms. Clinical breast examination may improve early diagnosis directly by finding breast cancers at earlier stages or indirectly by heightening women's awareness of breast health concerns.To investigate factors that influence time to presentation and stage at diagnosis among patients with breast cancer to determine whether history of previous clinical breast examination is associated with earlier presentation and/or earlier cancer stage at diagnosis.In this cross-sectional analysis of individual patient interviews using a validated Breast Cancer Delay Questionnaire, 113 (71.1%) of 159 women with breast cancer treated at a federally funded tertiary care referral cancer center in Trujillo, Peru, from February 1 through May 31, 2015, were studied.Method of breast cancer detection and factors that influence time to and stage at diagnosis.Of 113 women with diagnosed cancer (mean [SD] age, 54 [10.8] years; age range, 32-82 years), 105 (92.9%) had self-detected disease. Of the 93 women for whom stage was documented, 45 (48.4%) were diagnosed with early-stage disease (American Joint Committee on Cancer [AJCC] stage 0, I, or II), and 48 (51.6%) were diagnosed with late-stage disease (AJCC stage III or IV). Mean (SD) total delay from symptom onset to initiation of treatment was 407 (665) days because of patient (mean [SD], 198 [449] days) and health care system (mean [SD], 241 [556] days) delay. Fifty-two women (46.0%) had a history of clinical breast examination, and 23 (20.4%) had undergone previous mammography. Women who underwent a previous clinical breast examination were more likely to have shorter delays from symptom development to presentation compared with women who had never undergone a previous clinical breast examination (odds ratio, 2.92; 95% CI, 1.30-6.60; P = .01). Women diagnosed with shorter patient delay were more likely to be diagnosed with early-stage disease (AJCC stage 0, I, or II) than those with longer patient delay (31 [58.5%] vs 11 [30.6%], P = .01). Women who underwent a previous clinical breast examination were more likely to be diagnosed with early-stage disease compared with women who had never undergone previous clinical breast examination; this relationship remained significant after controlling for insurance and household income (odds ratio, 2.44; 95% CI, 1.01-5.95; P = .048).In a population in which most breast cancers are self-detected, previous clinical breast examination was associated with shorter patient delay and earlier stage at breast cancer diagnosis. In regions of the world that lack mammographic screening, the routine use of clinical breast examination may provide a resource-appropriate strategy for improving breast cancer early diagnosis.
Evaluation de la prise en charge endoscopique des fistules après chirurgie bariatrique dans un centre tertiaire
Authors: H Benosman, G Rahmi, E Samaha, A Vienne, M Bruzzi, C Lorenceau-Savale, S Khater, F Zinzindouhe, JM Chevallier, R Douard, A Berger, C Cellier
Journal: Endoscopy (2016)

La chirurgie bariatrique se complique dans 2 à 7% des cas d'une fistule digestive, associée à une morbidité élevée. Sa prise en charge endoscopique est mal codifiée. Notre objectif était d'évaluer le taux et le délai de fermeture des fistules post sleeve gastrectomie ou by-pass gastrique après un traitement endoscopique.
Abstract P055: 2-Deoxy-Glucose Reduces Doxorubicin Cardiotoxicity in Tumor-Bearing Mice
Authors: Derek Timm, Michelle Phillips, Allison Haugrud, Yongxian Zhuang, Keith Miskimins, Qiangrong Liang
Journal: Circulation Research (2011)

Doxorubicin (DOX) is a potent, commonly used anthracycline antibiotic for a wide range of cancers, but its dose is limited by its strong cardiotoxic effects. The glucose analog 2-deoxy-D-glucose (2-DG) has been shown to enhance the antitumor efficacy of DOX in tumor cell lines and in animals. However, the cardiac effects of 2-DG in these experiments were not determined. In the current study, we examined whether 2-DG could protect from DOX cardiotoxicity in a BALB/c mouse breast cancer model. A total of 32 mice were injected with 10 5 4T1 mouse mammary epithelial tumor cells in the right hind leg. The tumor was allowed to progress for 1 week before dividing the mice into four groups: saline, 2-DG, DOX, and 2-DG with DOX treatment. 2-DG was given 150 mg/kg i.p. Monday through Friday; DOX was given 5 mg/kg i.p. Wednesday. The study was conducted for 3 weeks and echocardiography was performed the day before sacrifice. Two of the eight mice in the DOX group died before echocardiography, while none died in the 2-DG with DOX group. Echocardiography indicated similar cardiac function between saline and 2-DG groups as measured by fractional shortening (36.3±1.31% vs 37.7±0.942%, p&gt;0.05). DOX markedly reduced cardiac function, which was almost completely recovered by 2-DG (25.1±1.06% vs 36.7±1.76%, p&lt;0.01). Serum CK-MB content, a common clinical marker for heart damage, was increased ~6 fold in the DOX group (67.5±19.4 vs 400±145, p&lt;0.023). 2-DG tended to reduce DOX-triggered CK-MB release, but it did not reach significant levels likely due to the small sample size and high variation (279±68.7 vs 400±145, p&gt;0.05). Nonetheless, 2-DG largely eliminated DOX-induced apoptosis in the heart as shown by a DNA laddering assay. 2-DG or DOX alone increased cardiac autophagic flux as measured by the difference in LC3-II protein levels in the absence and presence of the lysosomal inhibitor, bafilomycin A1. Paradoxically, autophagic flux was not notably elevated when mice were treated with 2-DG and DOX simultaneously. These results demonstrate the ability of 2-DG to reduce DOX cardiotoxicity without affecting its antitumor activity, suggesting that 2-DG can improve the therapeutic window for DOX, allowing greater flexibility in designing different regimens for treating cancers.
Changes in measures of cervical, vestibular, dynamic balance and tasks of divided attention following sport-related concussions in elite youth ice hockey players
Authors: Kathryn J Schneider, Luz Palacios-Derflingher, Willem H Meeuwisse, Carolyn A Emery
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate acute changes in measures of cervical spine, vestibulo-ocular reflex (VOR) function, dynamic balance and tasks of divided attention in elite youth ice hockey players following a sport-related concussion. Study Design Prospective Case series Setting Sport Medicine Centre, Calgary, Alberta, Canada Participants Five hundred and fifty-nine (474 males) elite (AA and AAA) Bantam (13-14 years) and Midget (15-17 years) youth ice hockey players. Outcome measures Clinical measurements including cervical flexor endurance test (CFE), head perturbation test, head thrust test, dynamic visual acuity (DVA) (clinical and computerised), Functional Gait Assessment (FGA) and Walking While Talking (WWTT) test at baseline and acutely following concussion. Main results Sixty-nine of 97 (71%) players completed both baseline and acute post concussion measures for their first concussion and were included in these analyses. Following concussion, neck pain, headache and dizziness increased in 42%, 58% and 40% of participants respectively. After Bonferroni corrections (α=0.00625), using Wilcoxon Signed-Rank Test, cervical spine measures were significantly worse following concussion compared to baseline [cervical flexor endurance test (z=−5.195, p&lt;0.001) and head perturbation test (z=−4.631, p&lt;0.001)]. Time to complete a complex task of divided attention (WWTT) relative to their normal walking speed was longer than baseline (z=−2.762, p=0.0057). There was no change in DVA or FGA following concussion. Conclusions Measures of cervical spine function and tasks of divided attention were worse following concussion. However, tests of VOR and dynamic balance were not significantly different than at baseline. Future research to evaluate the mechanism underlying these changes is warranted. Competing interests None.
Mining the National Cancer Institute’s drug screening database in search for antineoplastics that selectively target MDR1/P-glycoprotein-overexpressing cancer cells
Authors: Gergely Szakacs, Benjamin F. Chu, Joseph A. Ludwig, Michael M. Gottesman
Journal: Cancer Research (2006)

1250   The Developmental Therapeutic Program (DTP) of the National Cancer Institute (NCI) has generated a large database of cellular response patterns across sixty human cancer cell lines (NCI60). Analysis of an initial subset of the database restricted to 1,429 compounds identified a compound (NSC73306) whose activity was potentiated, rather than antagonized by the MDR1 multidrug transporter. This was surprising, since ABCB1 (MDR1-P-gp) is probably the best known mediator of resistance to anticancer drugs. In an effort to screen for compounds that behaved similarly, we have extended the analysis to include approximately 42,000 compounds tested on the NCI60 panel. Here we show that this pharmacogenomic approach is indeed suitable for the identification of “MDR1-inverse” compounds that show preferential toxicity in otherwise multidrug resistant, Pgp overexpressing cancer cells. Further evaluation of the compounds provided clues for a common mechanism of action, and suggested a putative pharmacophore. Therapy with enhanced efficacy in P-gp expressing cells offers a novel approach to overcome “classical” MDR by targeting cells most resistant to antineoplastic agents. Drugs that exploit hidden vulnerabilities of MDR cells may avoid the well-documented side-effects observed in clinical trials of “classical” P-gp inhibitors and may serve as leads for development of novel anti-cancer agents to treat resistant disease.
Immunotherapy with CpG-ODN in neoplastic meningitis: A phase I trial.
Authors: Renata Ursu, Sophie Taillibert, Dimitri Psimaras, Claire Banissi, Olivier Bailon, Emilie Le Rhun, Jean Sebastien Guillamo, Athina Marantidou, Khê Hoang-Xuan, Catherine Belin, Antoine F Carpentier
Journal: Journal of Clinical Oncology (2013)

3065^ Background: TLR9 agonists, such as phosphorothioate oligodeoxynucleotides containing CpG motifs (CpG-ODNs), are immunostimulating agents with antitumor effects in animal models. Neoplastic meningitis is a devastating disease, with no efficient therapeutic available. A phase I trial was conducted in patients with neoplastic meningitis to define the safety profile of subcutaneous injections, combined or not with intra-CSF administration of a CpG ODN. Methods: The diagnostic of neoplastic meningitis was based on a positive CSF cytology or on the association of clinical symptoms with meningeal enhancement on MRI. Cohorts of 3-6 patients were treated for 5 weeks with escalating doses of CpG-28 (level 1 and 2: 0.1and 0.3 mg/kg/week subcutaneously (sc); level 3 to 6: 0.3mg/kg sc associated with 3/7/12/18 mg intrathecally every other week). Concomittant treaments with radiotherapy or chemotherapy were allowed. The primary endpoint was tolerance. Secondary endpoints were time until neurological progression and survival. Results: Twenty-nine (29) patients were included. Primary cancer was malignant glioma (n=15), lung carcinoma (n=7), breast cancer (n=3), melanoma or melanocytoma (n=2), ependymoma (n=1), and colorectal cancer (n=1). At diagnosis median age was 56 years and median KPS was 70%. The treatment was well tolerated. Adverse effects possibly or probably related to the studied drug consisted in grade 2 lymphopenia, anemia and neutropenia (n=19), local erythema at injection sites (n=14), fever (n=10) and seizure (n=11). Two serious adverse events were considered as possibly or probably related to the protocol: one local infection and one intra-cerebral haemorrhage. Interestingly, median survival was higher in patients (n=8) who were concomitantly treated with bevacizumab a time of protocol (19 weeks vs 15 weeks, p=0.11). Conclusions: CpG-28 was well tolerated at doses up to 0.3mg/kg subcutaneously and 18 mg intrathecally. Main side effects were limited to local erythema, lymphopenia and fever. Combination with bevacizumab warrants further clinical investigations. Clinical trial information: P060301.
Subsidies for Oral Chemotherapy and Use of Immunomodulatory Drugs Among Medicare Beneficiaries With Myeloma
Authors: Adam J. Olszewski, Stacie B. Dusetzina, Charles B. Eaton, Amy J. Davidoff, Amal N. Trivedi
Journal: Journal of Clinical Oncology (2017)

Purpose The low-income subsidy (LIS) substantially lowers out-of-pocket costs for qualifying Medicare Part D beneficiaries who receive orally administered chemotherapy. We examined the association of LIS with the use of novel oral immunomodulatory drugs (IMiDs; lenalidomide and thalidomide) among beneficiaries with myeloma, who can receive either orally administered or parenteral (bortezomib-based) therapy. Methods Using SEER-Medicare data, we identified Part D beneficiaries diagnosed with myeloma in 2007 to 2011. In multivariable models adjusted for sociodemographic and clinical characteristics, we analyzed associations between the LIS and use of IMiD-based therapy, delays between IMiD refills, and select health outcomes during the first year of therapy. Results Among 3,038 beneficiaries, 41% received first-line IMiDs. Median out-of-pocket cost for the first IMiD prescription was $3,178 for LIS nonrecipients and $3 for LIS recipients, whereas the respective median costs for the first year of therapy were $5,623 and $6, respectively. Receipt of the LIS was associated with a 32% higher (95% CI, 16% to 47%) probability of receiving IMiDs among beneficiaries age 75 to 84 years and a significantly lower risk of delays between refills in all age groups (adjusted relative risk, 0.54; 95% CI, 0.32 to 0.92). Duration of therapy did not significantly differ between LIS recipients and nonrecipients (median, 7.6 months). Patients treated with IMiDs had significantly fewer emergency department visits and hospitalizations compared with patients receiving bortezomib (without IMiDs), but 1-year overall survival and cumulative Medicare costs were similar. Conclusion Medicare beneficiaries with myeloma who do not receive LISs face a substantial financial barrier to accessing orally administered anticancer therapy, warranting urgent attention from policymakers. Limiting out-of-pocket costs for expensive anticancer drugs like the IMiDs may improve access to oral therapy for patients with myeloma.
Diagnosis and management of inflammatory bowel disease in children
Authors: Stephanie B Oliveira, Iona M Monteiro
Journal: BMJ (2017)

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are lifelong conditions that often begin in childhood. The implications of IBD are of particular importance in children because of the potential negative effects on growth, development, psychosocial function, and overall wellbeing. The key management strategy is to achieve sustained control of intestinal inflammation and monitor for potential complications of the disease and side effects of therapies. Overall, the evidence on the management of IBD in children is less extensive than in adults, but good quality multicenter studies and various guidelines and society consensus statements are available. This review summarizes the evidence on the pathophysiology, diagnosis, and approaches to management of children and adolescents with IBD.
IS SHOE DROP A KEY FACTOR FOR INJURY PREVENTION IN RUNNING? PART 2: AN RCT ON RUNNING BIOMECHANICS
Authors: Daniel Theisen, Paul Gette, Nicolas Chambon, Axel Urhausen, Laurent Malisoux
Journal: British Journal of Sports Medicine (2017)

Background So far, only few biomechanical studies have specifically addressed the acute effect of the heel-to-toe drop in running shoes, but longitudinal studies are lacking. Objective Our aim was to investigate if the drop of conventional cushioned shoes induces specific long-term adaptations in running technique. Design Randomised controlled trial. Setting Leisure-time distance runners were tested on a treadmill at their preferred running speed before and after a 6-month period. Participants Study participants (n=59), unexperienced with minimalist shoes, were recruited via advertisements in local newspapers. Intervention The participants received a pair of running shoes with a drop of 10 mm (D10, n=20), 6 mm (D6, n=17) or 0 mm (D0, n=22). Apart from the shoe drop, the 3 versions were strictly identical. Main Outcome Measurements Kinematic and spatio-temporal variables of running trials were obtained using synchronized systems for three-dimensional motion analysis (200 Hz) and step cycle event detection. Joint angles were investigated at initial contact and mid-stance phase of 151±22 analysed steps per record. Two-way analysis of variance for repeated measures with the post hoc Bonferroni correction was used and accepted significance was set at p&lt;0.05. Results The participants performed on average a total of 332±178 km over 163±16 days between pre- and post-tests. No interaction between shoe drop and time was found for any of the spatio-temporal variables, or for any angles at initial contact. At mid-stance phase, a significant shoe drop by time interaction was found for knee abduction angle (p=0.032). For D0 group, knee abduction decreased (−0.3±3.1 vs. -1.3±2.6°) in contrast to D6 (0.3±2.7 vs. 1.3±3.1°) and D10 (−0.2±3.2 vs. 0.5±3.1°) groups. However, none of the pairwise comparisons was significant in the post-hoc analysis. Conclusions Shoe drop of standard cushioned shoes does not seem to influence long term adaptation in running biomechanics.
Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis
Authors: Johan Duchene, Igor Novitzky-Basso, Aude Thiriot, Maria Casanova-Acebes, Mariaelvy Bianchini, S Leah Etheridge, Elin Hub, Katrin Nitz, Katharina Artinger, Kathrin Eller, Jorge Caamaño, Thomas Rülicke, Paul Moss, Remco T A Megens, Ulrich H von Andrian, Andres Hidalgo, Christian Weber, Antal Rot
Journal: Nature Immunology (2017)