tbuckley/cabot-search huggingface dataset:
Identification of a novel peptide that targets bladder tumor cells in vivo and in the urine
Authors: Hai-Yan Hong, Seung-Min Lee, Tae-Gyun Kwon, Rang-Woon Park, In-San Kim, Byung-Heon Lee
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3089 

Bladder cancer is one of the most common tumors of genitourinary tract. Selective delivery of drugs to tumor tissues is important for effective tumor therapy. Here we identified a peptide targeting bladder tumor cells using phage display. A phage library containing CX7C random peptides was screened for selective binding to cells from human bladder tumor xenograft. Selected phage clones were individually evaluated for binding to cultured bladder tumor cells and for binding to cells from fresh human tumor tissues over cells from normal bladder tissues. The peptide displayed by the most promising clone was synthesized and designated as Bld-1. Fluorescein-conjugated Bld-1 peptide showed selective binding to frozen sections of human bladder tumor tissues, while little binding to normal bladder tissues was observed. In vivo tumor targeting was examined in a carcinogen-induced rat tumor model. When the fluorescent peptide was introduced into the bladder lumen, it selectively bound to tumor epithelium, while little binding was observed in normal bladder epithelium. Moreover, when the fluorescent peptide was intravenously injected into the tail vein, it homed to the bladder tumor, but was not detectable in normal bladder and control organs such as lung. The peptide co-localized in tumor tissue with cykokeratin, an epithelial cell marker. Next, we examined whether the peptide could be used to detect tumor cells in the urine. Fuorescent Bld-1 peptide bound to urinary cells collected from tumor patients, whereas little binding was observed in urinary cells from healthy individuals. The Bld-1 peptide may be a useful targeting moiety for selective delivery of therapeutics and also a diagnostic probe for the detection of bladder tumor in vivo and in the urine.
TRPA1 channels promote astrocytic Ca2+ hyperactivity and synaptic dysfunction mediated by oligomeric forms of amyloid-β peptide
Authors: Anthony Bosson, Adrien Paumier, Sylvie Boisseau, Muriel Jacquier-Sarlin, Alain Buisson, Mireille Albrieux
Journal: Molecular Neurodegeneration (2017)

Excessive synaptic loss is thought to be one of the earliest events in Alzheimer's disease (AD). However, the key mechanisms that maintain plasticity of synapses during adulthood or initiate synapse dysfunction in AD remain unknown. Recent studies suggest that astrocytes contribute to functional changes observed during synaptic plasticity and play a major role in synaptic dysfunction but astrocytes behavior and involvement in early phases of AD remained largely undefined.We measure astrocytic calcium activity in mouse CA1 hippocampus stratum radiatum in both the global astrocytic population and at a single cell level, focusing in the highly compartmentalized astrocytic arbor. Concurrently, we measure excitatory post-synaptic currents in nearby pyramidal neurons.We find that application of soluble Aβ oligomers (Aβo) induced fast and widespread calcium hyperactivity in the astrocytic population and in the microdomains of the astrocyte arbor. We show that astrocyte hyperactivity is independent of neuronal activity and is repaired by transient receptor potential A1 (TRPA1) channels blockade. In return, this TRPA1 channels-dependent hyperactivity influences neighboring CA1 neurons triggering an increase in glutamatergic spontaneous activity. Interestingly, in an AD mouse model (APP/PS1-21 mouse), astrocyte calcium hyperactivity equally takes place at the beginning of Aβ production, depends on TRPA1 channels and is linked to CA1 neurons hyperactivity.Our experiments demonstrate that astrocytes contribute to early Aβo toxicity exhibiting a global and local Ca2+ hyperactivity that involves TRPA1 channels and is related to neuronal hyperactivity. Together, our data suggest that astrocyte is a frontline target of Aβo and highlight a novel mechanism for the understanding of early synaptic dysregulation induced by soluble Aβo species.
REDX08608, a Novel, Potent and Selective, Reversible BTK Inhibitor with Efficacy and Equivalent Potency Against Wild-Type and Mutant C481S BTK
Authors: Nicolas E. S. Guisot, Stuart A. Best, Victoria Wright, Andrew Thomason, Jennifer A. Woyach, Rose Mantel, Fabienne McClanahan, Valentina Abet, Diana Castagna, Peggy Cousin, Juliette Emmerich, Kelvin Ho, James Russell Kelly, James King-Tours, Kristina Lyons, Melanie Muller, Julienne Refuerzo, Louise Sargent, Fatima Talab, Matilda Bingham, Caroline Phillips, Richard Armer
Journal: Blood (2016)
Vestibular and vision deficits following concussion in children under 12
Authors: Christina L Master, Allison E Curry, Ronni Kessler, Melissa R Pfeiffer, Matthew F Grady, Roni Robinson, Kristy B Arbogast
Journal: British Journal of Sports Medicine (2017)

Objective Vestibular and oculomotor visual (VOM) deficits are emerging as key characteristics of youth concussion. However, since most studies of paediatric concussion focus on adolescents, little is known about the extent to which younger children experience this deficit. To address this gap, we used an electronic health record (EHR) system across a large paediatric healthcare network to quantify the presence of VOM deficits following concussion in patients under age 12. Design Descriptive epidemiology. Setting Data were collected from all primary (n=31) and relevant specialty care (n=4) network settings. Participants We identified all patients aged 5–11 years who had ≥1 clinical visit for concussion at a network primary or specialty care site from 7/1/2014 through 6/30/2015. We included the 82% of these patients for whom a concussion electronic clinical decision support tool within the EHR was used during their initial visit. Outcome measures The proportion who demonstrated each VOM deficit – balance, saccades, gaze stability, and convergence – was calculated among all who were assessed for that deficit. Main results 871 patients were included (median [IQR]: 10 [8, 11] years). On physical examination, 58% had at least one VOM deficit. 44% had balance abnormalities, 39% had saccadic dysfunction, 28% had deficits in gaze stability, and 10% convergence insufficiency. Conclusions In this sample, vestibular oculomotor visual deficits following concussion in young children were common. Improved recognition of the deficits will lead to timely diagnosis and appropriate management, including school accommodations for oculomotor visual challenges and vestibular therapy for motion sensitivity issues. Competing interests None. KB, Arbogast serves as a consultant to the National Football League Players Association on head injury topics.
Preeclampsia and Fetal Congenital Heart Defects
Authors: Basky Thilaganathan
Journal: Circulation (2017)

uman placentation is uniquely associated with physiological remodeling of the maternal spiral arteries by the invading trophoblast to produce a lowresistance maternal uterine circulation.The current paradigm considers defective placentation as the cause of preeclampsia, especially the preterm variety of the disorder. 1Related persistence of a high-resistance maternal uterine circulation, impaired placental perfusion, and maternal antiangiogenic stress response are all considered to be involved in the pathogenesis of preeclampsia. 1 An angiogenic imbalance has also previously been noted in association with developmental defects of the human fetal heart. 2 In this issue of Circulation, Boyd and colleagues 3 used these observations as the rationale for investigating the relationships between preeclampsia and fetal congenital heart defects in a cohort of almost 2 million Danish pregnancies.The cohort included ≈18 000 fetuses with congenital heart defects and 55 000 pregnancies complicated by preeclampsia. RELATIONSHIP BETWEEN PREECLAMPSIA AND FETAL CONGENITAL HEART DEFECTSWomen carrying a fetus with a congenital heart defect, regardless of the type of defect, had a 7-fold increase in the risk of early preeclampsia before <34 weeks' gestation.There is a definable dose-response curve with the risk decreasing, with later preeclampsia down to a 16% increase in preeclampsia at term and no association with gestational hypertension.The relationship between fetal congenital cardiac defects and an increased risk of maternal preeclampsia has been noted previously and attributed to the commonality of shared angiogenic imbalance in the mother and fetus. 4,5The novel findings of the present study are that in a subcohort of 700 000 women with ≥2 pregnancies, women who previously had a child with a congenital cardiac defect had a 2-fold greater risk of early preeclampsia and a 25% greater risk of term preeclampsia.Conversely, early preeclampsia in a previously pregnancy was associated with a 6-fold increased risk of offspring congenital heart defects in the current pregnancy.These observations deserve further exploration because they are of significant clinical and biological relevance. CLINICAL RELEVANCE OF THE INCREASED RISK FOR FETAL CONGENITAL CARDIAC DEFECTSAccurate and early diagnosis of fetal congenital heart defects in pregnancy is now feasible in a routine setting and has been shown to have a noticeable effect on the subsequent outcome of pregnancy. 6Internationally, detailed fetal echocardiog- Preeclampsia and Fetal Congenital Heart DefectsSpurious Association or Maternal Confounding?
Major Bleeding in Patients With Diabetes and Atrial Fibrillation Treated With New Oral Anticoagulants
Authors: Alina Scridon
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Clinical impact of renal impairment on safety in elderly colon cancer patients receiving capecitabine plus oxaliplatin as adjuvant therapy; multicenter post-marketing surveillance study
Authors: Kentaro Yamazaki, Shigemi Matsumoto, Chiyo K. Imamura, Chiemi Yamagiwa, Ayaka Shimizu, Takashi Tamura, Takayuki Yoshino
Journal: Annals of Oncology (2017)
Characteristics, treatment, and outcomes of patients with de novo HR+/HER2- advanced breast cancer: A retrospective chart review of community-based oncology practices.
Authors: Peggy L. Lin, Alexander R. Macalalad, Yanni Hao, James E. Signorovitch, Eric Qiong Wu, Zhou Zhou, Jinlin Song, Erika Ohashi, Caroline Kelley, Suleiman Alfred Massarweh
Journal: Journal of Clinical Oncology (2014)

e11516 Background: The majority of patients presenting with hormone receptor-positive (HR+), human epidermal growth factor receptor-negative (HER2-) advanced breast cancer (aBC) ultimately experience progression after 1st-line therapy. This study describes the characteristics, treatment patterns and outcomes of de novo aBC patients following progression on 1st-line therapy. Methods: Medical charts were reviewed for woman with HR+/HER2- de novo aBC treated in a community oncology network. Included patients had a 1st progression (index progression) between 1/1/2004 and 9/30/2010 after initiating 1st-line aBC treatment and no prior adjuvant treatment for aBC. The study was approved by the jurisdictional Institutional Review Board. Information was collected on patient demographics, metastases, treatment types and durations, and death. Kaplan-Meier analysis was used to estimate overall survival. Results: We studied 112 patients with de novo aBC who experienced progression on 1st-line treatment. At the time of 1st-line initiation, metastatic disease was present in the bone (50% of patients), lymph nodes (32%), liver (17%), lung (13%), other viscera (6%) and other sites (14%). 81% of patients received endocrine therapy as 1st-line treatment for aBC, with the remainder receiving chemotherapy or other therapies. Among those receiving 1st-line endocrine therapy, 38% received anatrozole, 34% letrozole, 26% tamoxifen, 10% exemestane, and 8% fulvestrant. At the time of index progression, the mean age was 60.8 years and the median Charlson Comorbidity Index (CCI) was 2. The median time from initiating 1st-line aBC treatment to first disease progression was 10.5 months. 83% (n=93) died during the study period with a median overall survival following the index progression of 21.6 months. Conclusions: Among patients with HR+/HER2- de novo aBC treated in community practice, the median duration of 1st-line treatment was less than a year, with 81% receiving endocrine therapy. Median overall survival from the first progression after initiating 1st-line treatment for aBC was less than 2 years.
The Department of Health's view
Authors: Barry Cockcroft, Liam Donaldson
Journal: BMJ (2007)

Cheng et al's article on fluoridation of water supplies provides a welcome opportunity to restate our view that fluoridation has reduced the burden of dental disease and offers the potential to address persistent inequalities in oral health.1 As with other health measures, safety should continue to be monitored and the ethical dimension discussed.

We first address the doubts expressed about the Department of Health's objectivity. The Department of Health, in 1999, commissioned the University of York to undertake a systematic review of fluoridation.2 The York team considered 735 research studies that met their relevance criteria and found no conclusive evidence of a causal …
Prognostic value of primary tumor location in stage III colon cancer is associated with RAS and BRAF mutational status.
Authors: Julien Taieb, Raphael Kourie Hampig, François Emile Jean, Karine Le Malicot, Ralyath Balogoun, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Luc Van Laethem Jean, Claire Mulot, Olivier Bouché, Thomas Aparicio, Pierre Michel, Josef Thaler, John Bridgewater, Eric Van Cutsem, Géraldine Perkins, Come Lepage, Ramon Salazar, Pierre Laurent Puig
Journal: Annals of Oncology (2017)
Abstract 11752: Prognostic Value of Neutrophil to Lymphocyte Ratio in Patients Admitted With Acute Decompensated Heart Failure; A Comparison With Platelet to Lymphocyte Ratio and Glasgow Prognostic Score
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Masashi Ishimi, Hideyuki Hakui, Tatsuhisa Ozaki, Yoshihiro Satoh, Masahiro Seo, Masatake Fukunami
Journal: Circulation (2015)

Backgrounds: Inflammation plays a critical role in the outcomes of heart failure. As indicators of the systemic inflammatory response, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been proposed to predict the poor outcome in patients (pts) with acute coronary syndrome. Furthermore, as another systemic inflammation-based score, the Glasgow Prognostic Score (GPS) has recently been reported to provide prognostic information in pts with heart failure. However, there is no information available on the comparison of prognostic impacts of these systemic inflammatory indices in pts admitted with acute decompensated heart failure (ADHF). Methods and Results: We studied 305 consecutive ADHF pts discharged with survival. At the admission and discharge, NLR and PLR were measured and GPS (0,1 and 2) was also obtained by combining elevated CRP (&gt;1mg/dl) and hypoalbuminemia(&lt;3.5g/dl) (none=0, either=1, and both=2). During a follow up period of 4.2±3.3 yrs, 96 pts died. Neither NLR nor PLR at the admission showed an association with mortality. At multivariate Cox analysis, NLR at the discharge (p=0.01) was significantly associated with mortality, independently of age, systolic blood pressure, prior heart failure hospitalization, and serum sodium level, although PLR (p=0.01) and GPS (p=0.02) at the discharge showed a significant association with mortality at univariate analysis. By ROC analysis, AUC of NLR at the discharge was 0.705 (0.639-0.772, p&lt;0.0001), which was greater than those of PLR (0.615[0.544-0.687], p=0.002) and GPS (0.567[0.490-0.644], p=0.09) at the discharge. Pts with highest tertile of NLR (&gt;2.2) had a increased risk of mortality than middle tertile (NLR=2.2-1.5; HR 2.0 [1.3-3.3]) and lowest tertile (NLR&lt;1.5: HR 4.4 [2.5-7.9]). Conclusion: NLR at the discharge provides more valuable prognostic value for the prediction of total mortality than PLR and GPS in ADHF pts.
A model for Hepatitis C Virus (HCV) Expression in Cell Culture
Authors: P Sheehy, M Scallan, E Kenny-Walsh, F Shanahan, LJ Fanning
Journal: Endoscopy (2006)

HCV is a single-stranded, positive sense, RNA virus. Assessment and development of novel anti-viral treatments for HCV infection has been hampered by the lack of an efficient cell culture model. However, recently attention has turned to the development of models whereby the replication of HCV can be studied in cell culture. The aim of this study was to construct a novel tetracycline-regulated model for the investigation of an Irish HCV isolate in cell culture. A novel tetracycline-regulated HCV cDNA plasmid was constructed. HCV core protein/RNA were detected in a tetracycline-regulated manner in cell culture and HCV RNA was processed from the HCV cDNA plasmid at defined termini. In addition, Interferon-alpha-2b decreased HCV expression to undetectable levels. Firstly, this HCV expression model adds significantly to the growing pool of HCV replication models currently available and represents the HCV infection of a globally unique Irish population. Secondly, this HCV expression model may be used to investigate the influence of HCV on the host cell by direct comparison of HCV expression in an on/off environment. Finally, this novel tetracycline-regulated cDNA plasmid may be a useful tool for the in vitro expression of full-length genomes of other RNA viruses including Dengue and Yellow Fever virus.
Doctors commended for their bravery in response to terrorist incidents
Authors: Anne Gulland
Journal: BMJ (2017)

Two doctors have been commended for “running towards danger” in response to terrorist incidents in London and Manchester.12

Jeeves Wijesuriya, a GP trainee and chair of the BMA Junior Doctors’ Committee, and Michael Daley, a consultant anaesthetist in Manchester, who were first on the scenes of the attacks were entered into the BMA’s book of valour in a ceremony at this week’s annual representative meeting in Bournemouth. The book is a recognition of distinguished service and …
Functional GSTA1 Haplotypes Affect Clearance and Toxicity of Busulfan When Administered in 16 Doses to Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation: A Multicenter Prospective Study on Behalf of the Pediatric Disease Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Marc Ansari, Patricia Huezo-Diaz, Chakradhara Rao Satyanarayana Uppugunduri, Tiago Nava, Mohammed Aziz Rezgui, Vid Mlakar, Laurence Lesne, Yves Theoret, Yves Chalandon, L Lee Dupuis, Tal Schechter, Imke H Bartelink, Jaap Jan Boelens, R.G.M. Bredius, Jean-Hugues Dalle, Saba Azarnoush, Petr Sedlacek, Victor A. Lewis, Martin Champagne, Christina Peters, Henrique Bittencourt, Maja Krajinovic
Journal: Blood (2016)
Colonic Stents for Palliation of Malignant Colorectal Obstruction
Authors: SJ Murphy, U Pallikona, H Calvert, K McCallion, TCK Tham
Journal: Endoscopy (2006)

Aims: Colonic stents are used to palliate inoperable malignant colorectal disease but outcome data are sparse. We analysed our experience with colonic stents, particularly with respect to complications and survival.
DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions
Authors: Manuel Buscarlet, Sylvie Provost, Yassamin Feroz Zada, Amina Barhdadi, Vincent Bourgoin, Guylaine Lépine, Luigina Mollica, Natasha Szuber, Marie-Pierre Dubé, Lambert Busque
Journal: Blood (2017)
Cup size and nipple-sparing mastectomy.
Authors: Sunny D. Mitchell, Shawna C. Willey, Sheldon M. Feldman, Peter D. Beitsch, Gary Walter Unzeitig, Donna Marie Manasseh
Journal: Journal of Clinical Oncology (2014)

e12021 Background: We performed a preliminary analysis of the American Society of Breast Surgeons (ASBS) Nipple Sparing Mastectomy Registry (NSMR) to assess preoperative breast size, as measured by cup size, and feasibility of a nipple sparing mastectomy. Methods: The ASBS NSMR is a prospective, IRB approved, non-randomized multi-institutional registry assessing surgical techniques, utilized metrics, oncologic outcome, and aesthetic outcome of nipple sparing mastectomies. The registry has been open for 30 months. The target accrual is 1,000 individuals. Fifty five surgeons from 44 institutions are participating in the ASBS NSMR. A total of 471 patients underwent 780 mastectomies with indications of cancer (339), prophylaxis (440), and unknown (10). We specifically analyzed the preoperative cup size, identified as A,B,C, or D/D+ of individuals who underwent a nipple sparing mastectomy. The group of D/D+ includes 2 mastectomies with cup size E. Results: Nipple sparing mastectomies were performed on individuals with cup sizes A,B,C, D/D+ via a variety of incisions utilizing multiple reconstruction techniques. Incisions utilized included: inframammary, periareolar ellipse or hemi batwing, previous lumpectomy scar, previous mastopexy scar, radial incision, radial with periareolar extension, or wise mastopexy incision. Reconstruction techniques included DIEP, Latissimus dorsi flap, permanent implant, TRAM, or tissue expander. Infection rates were low (4.7%) and not correlated to cup size. Patient satisfaction ratings were available on 457 NSMs: Excellent (271), Good (149), Fair (37). Cosmetic outcome evaluations by the surgeon were available on 492 of the NSMs: Excellent (309), good (157) and Fair (26). Conclusions: A nipple sparing mastectomy with immediate reconstruction may be successfully performed on breasts with cup sizes of A,B,C, D/ D+, via a variety of incisions utilizing multiple reconstruction techniques. Rates of postoperative infection are low in each cup size. Patient satisfaction as well as cosmetic outcome was most consistently rated as excellent or good.
Marshaling FDA Benefit-Risk Expertise to Address the Current Opioid Abuse Epidemic
Authors: Scott Gottlieb, Janet Woodcock
Journal: JAMA (2017)

In this Viewpoint, FDA Commissioner Scott Gottlieb and CDER Director Janet Woodcock discuss how the FDA weighs the risks and benefits of opioids and integrates public health and clinical perspectives into decisions about opioid approval, marketing, restrictions, and labeling.
Continuous Cytarabine Plus Dexamethasone in Consolidation Phase to Patients with Childhood ALL: Result from Japan Association of Childhood Leukemia Study - JACLS ALL02 Protocol -
Authors: So-ichi Suenobu, Ikuya Usami, Toshihiko Imamura, Hirohide Kawasaki, Keiko Yumura Yagi, Shinichiro Nishimura, Makoto Kaneda, Yoshihiro Takahashi, Daiichiro Hasegawa, Nobuhiro Suzuki, Yoshiko Hashii, Takao Deguchi, Saito Akiko, Koji Kato, Yoshiyuki Kosaka, Mikiya Endo, Akihiro Iguchi, Megumi Oda, Hiroki Hori, Atsushi Sato, Tatsutoshi Nakahata, Tooru Kudoh, Junichi Hara, Keizo Horibe
Journal: Blood (2016)