tbuckley/cabot-search huggingface dataset:
Smart biomaterials: Surfaces functionalized with proteolytically stable osteoblast-adhesive peptides
Authors: Annj Zamuner, Paola Brun, Michele Scorzeto, Giuseppe Sica, Ignazio Castagliuolo, Monica Dettin
Journal: Bioactive Materials (2017)

Engineered scaffolds for bone tissue regeneration are designed to promote cell adhesion, growth, proliferation and differentiation. Recently, covalent and selective functionalization of glass and titanium surfaces with an adhesive peptide (HVP) mapped on [351-359] sequence of human Vitronectin allowed to selectively increase osteoblast attachment and adhesion strength in in vitro assays, and to promote osseointegration in in vivo studies. For the first time to our knowledge, in this study we investigated the resistance of adhesion sequences to proteolytic digestion: HVP was completely cleaved after 5 h. In order to overcome the enzymatic degradation of the native peptide under physiological conditions we synthetized three analogues of HVP sequence. A retro-inverted peptide D-2HVP, composed of D amino acids, was completely stable in serum-containing medium. In addition, glass surfaces functionalized with D-2HVP increased human osteoblast adhesion as compared to the native peptide and maintained deposition of calcium. Interestingly, D-2HVP increased expression of IBSP, VTN and SPP1 genes as compared to HVP functionalized surfaces. Total internal reflection fluorescence microscope analysis showed cells with numerous filopodia spread on D-2HVP-functionalized surfaces. Therefore, the D-2HVP sequence is proposed as new osteoblast adhesive peptide with increased bioactivity and high proteolytic resistance.
Evaluation of Mortality during Treatement of Acute Myeloid Leukemia in Patients According to Morocco National AML-MA-2011 Protocol in Casablanca
Authors: Romaric Massi, Mouna Lamchahab, Bienvenu Houssou, Nisrine Khoubila, Siham Cherkoui, Meryem Qachouh, Mohamed Rachid, Abdallah Madani, Uma H. Athale, Asmaa AQ Quessar
Journal: Blood (2016)
British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017
Authors: C.H. Smith, Z.K. Jabbar‐Lopez, Z.Z. Yiu, T. Bale, A.D. Burden, L.C. Coates, M. Cruickshank, T. Hadoke, E. MacMahon, R. Murphy, C. Nelson‐Piercy, C.M. Owen, R. Parslew, E. Peleva, E. Pottinger, E.J. Samarasekera, J. Stoddart, C. Strudwicke, V. A. Venning, R.B. Warren, L.S. Exton, M.F. Mohd Mustapa, P.M. McHenry, K. Gibbon, D.A. Buckley, T.A. Leslie, E.C. Mallon, S. Wakelin, S. Ungureanu, R.Y.P. Hunasehally, M. Cork, G.A. Johnston, J. Natkunarajah, F.S. Worsnop, N. Chiang, G. Petrof, J. Donnelly, C. Saunders, A.G. Brain
Journal: British Journal of Dermatology (2017)

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Unusual Presentation of Relapse in Neuroblastoma
Authors: Maria Felicia Villani, Maria Luisa D’Andrea, Aurora Castellano, Milena Pizzoferro, Maria Carmen Garganese
Journal: Clinical Nuclear Medicine (2017)

Neuroblastoma is the most common extracranial solid tumor in children and accounts for 8% to 10% of all childhood cancers. The spread of metastases is both lymphatic and hematogenous. Hematogenous route occurs most commonly in bone marrow and cortical bone; pancreatic metastases are very rare, and there are few reports about this topic in medical literature. We report the case of a 14-year-old boy who suffers a third relapse of neuroblastoma: in this patient I-MIBG confirms that lesions detected by CT were due to a relapse in pancreatic tissue and influenced subsequent therapeutic management.
Abstract 12131: Mechanism of Hypokalemia-dependent Arrhythmias in a New Porcine Model of Advanced Heart Failure: Insights Into the Pathophysiology of Increased Afterload in Chronic Myocardial Infarction
Authors: Kiyotake Ishikawa, Chaoqin Xie, Lukas J Motloch, Jaume Aguero, Jun Hu, Lauren Leonardson, Kenneth M Fish, Roger J Hajjar, Fadi G Akar
Journal: Circulation (2015)

Introduction: Hypertension worsens the prognosis of post-myocardial infarction (MI) patients. To examine the underlying mechanisms, we developed a new porcine model of post-MI heart failure with chronically increased afterload (HF/iAL). We identified the mode-of-initiation and mechanism-of-arrhythmias in this model, which accounts for arterial hypertension observed in a significant proportion of post-MI patients. Methods and Results: Yorkshire pigs underwent aortic banding 1-month following large anterior MI, and were allowed to survive for another 2-months. Aortic banding resulted in 1.3-fold increase in systemic vascular resistance index. HF/iAL pigs presented with mildly decreased left ventricular ejection fraction without significant changes in the end-diastolic and end-systolic volume indexes. Pressure-volume relationship during the preload reduction study revealed stiffer left ventricle in the HF/iAL pigs consistent with remote non-ischemic myocardial hypertrophy found in macroscopic and histological assessment. Increased afterload in HF/iAL pigs also led to a major increase in interstitial fibrosis in non-ischemic remote areas. HF/iAL pigs were highly prone to pacing-induced VT/VF, specifically under conditions of hypokalemia. Investigation of the electrophysiological substrate revealed the dependence of hypokalemia-mediated arrhythmias on conduction rather than repolarization abnormalities. HF/iAL pigs exhibited conduction slowing down to critical levels that were not achieved in normal preparations. Altered rate-dependent kinetics of conduction slowing in HF/iAL were consistent with a higher safety margin for successful propagation of abnormally slow wavefronts that gave rise to reentrant activity. Conclusions: Increased afterload in the post-MI heart is associated with cellular hypertrophy, widespread interstitial fibrosis, and increased ventricular stiffness. These changes predispose patients to congestive HF and promote reentrant arrhythmias during hypokalemia by facilitating the successful propagation of critically-slow wavefronts. Our findings reveal a novel mechanism by which non-K sparing diuretics promote lethal arrhythmias in hypertensive post-MI patients.
Ablation therapy for atrial fibrillation (AF) Past, present and future
Authors: P Jaïs
Journal: Cardiovascular Research (2002)

Atrial fibrillation, the most common arrhythmia, is frequently disabling and drug resistant. Non-pharmacological approaches including surgery and catheter-based ablation have been developed for the most symptomatic patients. These new treatment strategies have dramatically increased our knowledge of the pathophysiology of this arrhythmia but most importantly demonstrated that atrial fibrillation is curable. These approaches are far from being perfect but good enough to be offered in routine practice to selected patients in experienced centers. The importance of pulmonary veins in the initiation of AF has clearly been demonstrated and their role in maintaining AF is likely. Most of the curative approaches are therefore based on their isolation. Future technical improvements based on presently applied concepts are likely to widen the indications for ablation therapy of AF.
The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development
Authors: Masaki Miyazaki, Kazuko Miyazaki, Kenian Chen, Yi Jin, Jacob Turner, Amanda J. Moore, Rintaro Saito, Kenichi Yoshida, Seishi Ogawa, Hans-Reimer Rodewald, Yin C. Lin, Hiroshi Kawamoto, Cornelis Murre
Journal: Immunity (2017)
A single community center’s experience with abiraterone using strict PCWG2 definition of progression of disease.
Authors: Thomas Andrew Longo, Luke T. Nordquist
Journal: Journal of Clinical Oncology (2014)

e16093 Background: Abiraterone, an androgen synthesis inhibitor, has been successfully used in the treatment of castration-resistant prostate cancer (CRPC). The Prostate Cancer Work Group (PCWG2) has cautioned that patients should not be taken off therapy until the patient has completed at least 12 weeks. It has been the practice in our center to closely follow these guidelines and complete 12 weeks of therapy. We examined the PSA behavior during these first weeks of treatment. Methods: Clinical data were retrospectively analyzed for prostate-specific antigen (PSA), and the PSA doubling time was calculated in those patients who did not experience a decline in PSA. Those with a response were calculated for a percentage of decline. Results: A total of 55 patient charts qualified for review; only 49 charts had sufficient data for our calculations. 32 patients experienced a decline in their PSA, while 17 experienced a rise during the first 12 weeks of therapy. The PSA doubling time was increased in 14 out of the 17 with a rise in PSA. 6 patients had a decline of 0-30%, 6 had a decline of 30-50%, and 20 had a response greater than 50%. Conclusions: Abiraterone is a novel, noncytotoxic hormone therapy, and the PSA appears to have a novel response. Although a PSA decline is seen in only two thirds of the patients, almost every patient without a decline did have an increase in their doubling time. This suggests that the drug is active. Given that the intention is no longer to cure prostate cancer, but rather slow progression, patients may have their therapy inappropriately stopped if based on PSA response alone, particularly in the first 12 weeks. Our experience follows and supports the PCWG2 definition and hopefully will maximize the benefit and duration of each therapy.
Using Molecular Characterization to Support Investigations of Aquatic Facility–Associated Outbreaks of Cryptosporidiosis — Alabama, Arizona, and Ohio, 2016
Authors: Michele C. Hlavsa, Dawn M. Roellig, Matthew H. Seabolt, Amy M. Kahler, Jennifer L. Murphy, Taishayla K. McKitt, Evelyn F. Geeter, Ron Dawsey, Sherri L. Davidson, Thuy N. Kim, Theresa H. Tucker, Sally Ann Iverson, Brenna Garrett, Nicole Fowle, Jennifer Collins, Gregory Epperson, Scott Zusy, Joli R. Weiss, Ken Komatsu, Edwin Rodriguez, J. Gage Patterson, Rebecca Sunenshine, Brandi Taylor, Katie Cibulskas, Lynn Denny, Keoni Omura, Boris Tsorin, Kathleen E. Fullerton, Lihua Xiao
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Cryptosporidiosis is a nationally notifiable gastrointestinal illness caused by parasitic protozoa of the genus Cryptosporidium, which can cause profuse, watery diarrhea that can last up to 2-3 weeks in immunocompetent patients and can lead to life-threatening wasting and malabsorption in immunocompromised patients. Fecal-oral transmission of Cryptosporidium oocysts, the parasite's infectious life stage, occurs via ingestion of contaminated recreational water, drinking water, or food, or following contact with infected persons or animals, particularly preweaned bovine calves (1). The typical incubation period is 2-10 days. Since 2004, the annual incidence of nationally notified cryptosporidiosis has risen approximately threefold in the United States (1). Cryptosporidium also has emerged as the leading etiology of nationally notified recreational water-associated outbreaks, particularly those associated with aquatic facilities (i.e., physical places that contain one or more aquatic venues [e.g., pools] and support infrastructure) (2). As of February 24, 2017, a total of 13 (54%) of 24 states reporting provisional data detected at least 32 aquatic facility-associated cryptosporidiosis outbreaks in 2016. In comparison, 20 such outbreaks were voluntarily reported to CDC via the National Outbreak Reporting System for 2011, 16 for 2012, 13 for 2013, and 16 for 2014. This report highlights cryptosporidiosis outbreaks associated with aquatic facilities in three states (Alabama, Arizona, and Ohio) in 2016. This report also illustrates the use of CryptoNet, the first U.S. molecularly based surveillance system for a parasitic disease, to further elucidate Cryptosporidium chains of transmission and cryptosporidiosis epidemiology. CryptoNet data can be used to optimize evidence-based prevention strategies. Not swimming when ill with diarrhea is key to preventing and controlling aquatic facility-associated cryptosporidiosis outbreaks (https://www.cdc.gov/healthywater/swimming/swimmers/steps-healthy-swimming.html).
Effectiveness of an intervention to facilitate prompt referral to memory clinics in the United Kingdom: Cluster randomised controlled trial
Authors: Gill Livingston, Gianluca Baio, Andrew Sommerlad, Simon de Lusignan, Spyridon Poulimenos, Steve Morris, Greta Rait, Juanita Hoe
Journal: PLoS Medicine (2017)

Background Most people with dementia do not receive timely diagnosis, preventing them from making informed plans about their future and accessing services. Many countries have a policy to increase timely diagnosis, but trials aimed at changing general practitioner (GP) practice have been unsuccessful. We aimed to assess whether a GP's personal letter, with an evidence-based leaflet about overcoming barriers to accessing help for memory problems—aimed at empowering patients and families—increases timely dementia diagnosis and patient presentation to general practice. Methods and finding Multicentre, cluster-randomised controlled trial with raters masked to an online computer-generated randomisation system assessing 1 y outcome. We recruited 22 general practices (August 2013–September 2014) and 13 corresponding secondary care memory services in London, Hertfordshire, and Essex, United Kingdom. Eligible patients were aged ≥70 y, without a known diagnosis of dementia, living in their own homes. There were 6,387 such patients in 11 intervention practices and 8,171 in the control practices. The primary outcome was cognitive severity on Mini Mental State Examination (MMSE). Main secondary outcomes were proportion of patients consulting their GP with suspected memory disorders and proportion of those referred to memory clinics. There was no between-group difference in cognitive severity at diagnosis (99 intervention, mean MMSE = 22.04, 95% confidence intervals (CIs) = 20.95 to 23.13; 124 control, mean MMSE = 22.59, 95% CI = 21.58 to 23.6; p = 0.48). GP consultations with patients with suspected memory disorders increased in intervention versus control group (odds ratio = 1.41; 95% CI = 1.28, 1.54). There was no between-group difference in the proportions of patients referred to memory clinics (166, 2.5%; 220, 2.7%; p = .077 respectively). The study was limited as we do not know whether the additional patients presenting to GPs had objective as well as subjective memory problems and therefore should have been referred. In addition, we aimed to empower patients but did not do anything to change GP practice. Conclusions Our intervention to access timely dementia diagnosis resulted in more patients presenting to GPs with memory problems, but no diagnoses increase. We are uncertain as to the reason for this and do not know whether empowering the public and targeting GPs would have resulted in a successful intervention. Future interventions should be targeted at both patients and GPs. Trial registration Current Controlled Trials ISRCTN19216873
Abstract 154: Generation of Purified Cardiomyocytes from Pluripotent Stem Cells Using Molecular Beacons
Authors: Kiwon Ban, Brian Wile, Sangsung Kim, Jaemin Byun, Talib Saafir, Mary Wagner, Gang Bao, Young-Sup Yoon
Journal: Circulation Research (2012)

Background: While various methods for generating cardiomyocytes (CMs) from pluripotent stem cells (PSCs) including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been reported, all available methods are only allowed to produce heterogeneous population of CM mixed with non-CM cells. Therefore, strategies to enrich pure CMs for scientific and clinical applications have been highly required. Hence, we developed a novel system in which CMs can be purified by cardiac specific molecular beacons (MBs). MBs are dual-labeled antisense nano-scale probes that emit a fluorescence signal when hybridized to target mRNAs. We hypothesized that MBs targeted to CM specific mRNAs can identify CMs and allow isolation of purified CMs by fluorescence-activated cell sorting (FACS). Methods and results: Five MBs targeting distinct sites on either cardiac troponin T (cTNT) or α/β myosin heavy chain (α/βMHC) were designed and characterized in various cell types. To find the optimal MB that can selectively identifying CMs, each MB was delivered into HL-1 CMs, an immortalized mouse CM cell line, smooth muscle cells, endothelial cells, mouse ESCs and fibroblasts and its specificity was determined by flow cytometry. As a result, two MBs identified MB+ cells up to 98% from HL-1 CMs but lower than 10% of the non-CM cells suggesting these MBs are CM specific. Subsequently, the selected MBs were delivered into both mouse and human PSCs derived CMs and 41 to 49% of the cells were identified as an MB+ population. Interestingly, the rate of MB+ cells was similar to CM quantification determined by cTNT intracellular flow cytometry. Finally, we determined whether cell sorting with cardiac-specific MBs can enrich CMs from the heterogeneous mouse and human PSC cultures and found that ∼97% of MB-based sorted CMs expressed cTNT. These enriched cells were further cultured and their CM identity was verified by immunocytochemistry and qRT-PCR analysis. Ca2+ transient analysis further confirmed that these purified CMs displayed functional CM characteristics Conclusion: Using cardiac specific MBs, we were able to obtain highly purified CMs. These purified CMs and the system can be highly useful for clinical applications as well as drug discovery.
Adjuvant denosumab in breast cancer: Results from 3,425 postmenopausal patients of the ABCSG-18 trial.
Authors: Michael Gnant, Georg Pfeiler, Peter Christian Dubsky, Michael Hubalek, Richard Greil, Raimund Jakesz, Viktor Wette, Marija Balic, Ferdinand Haslbauer, Elisabeth Melbinger-Zeinitzer, Vesna Bjelic Radisic, Jonas C. S. Bergh, Florian Fitzal, Daniel Egle, Brigitte Mlineritsch, Guenther G. Steger, Susan Talbot, Douglas J Warner, Christian Fesl, Christian F. Singer
Journal: Journal of Clinical Oncology (2015)

504 Background: Adjuvant endocrine therapy compromises bone health in pre- and postmenopausal breast cancer (BC) patients. Treatment-induced osteopenia, osteoporosis, and fractures are frequent side effects particularly of aromatase inhibitors (AI). Anti-resorptive treatments such as bisphosphonates have been shown to prevent and counteract these side effects of endocrine therapy, and to potentially improve survival outcomes in postmenopausal BC patients. The aim of this trial was to investigate the effects of adjuvant anti-RANK-ligand Denosumab in postmenopausal patients with early hormone receptor+ (HR+) BC receiving AI treatment. Patients and Methods: 3,425 postmenopausal patients with HR+ BC receiving AI were recruited in 58 sites into this prospective, randomized, double-blind, placebo-controlled, phase-III trial. Patients were randomized 1:1 to either Denosumab 60mg or placebo q6mo s.c. The primary endpoint was time from randomization to first clinical fracture, secondary endpoints included outcome (DFS, OS) and bone effects (BMD changes, vertebral fractures). Results: Denosumab significantly delayed the time to first clinical fracture compared to placebo (HR = 0.5, 95% CI 0.39-0.65, p < 0.0001). The observed reduction in fractures between Denosumab and placebo arm (overall 92 vs 176) was similar in prognostic patient subgroups, e.g. in patients with normal bone health at baseline (n = 1,872, HR = 0.44, p < 0.0001) and in patients who started the trial already osteopenic (n = 1,548, HR = 0.57, p = 0.0021). Denosumab also significantly increased BMD of the lumbar spine (9.99%), total hip (7.88%) and femoral neck (6.49%) at 36 months (compared to placebo, all adjusted p-values < 0.0001). There were no differences between the Denosumab and placebo groups with respect to patient incidence adverse events (1366 vs 1334), or serious adverse events (521 vs 511). Despite proactive adjudication of potential ONJs by an independent expert panel, no ONJ case was observed. Conclusion: Adjuvant Denosumab significantly reduces fractures in postmenopausal BC patients receiving AI, and improves bone mineral density. Adjuvant Denosumab can be administered at this schedule with a favorable safety profile. Clinical trial information: NCT00556374.
Incidental Thyroid Nodule Noted on Intra-arterial Hepatic MAA Scan Before 90Y-SIRT
Authors: Sin-Di Lee, Chin Hu, Nan-Jing Peng
Journal: Clinical Nuclear Medicine (2017)

We report a case of a 61-year-old man who had recurrent hepatocellular carcinoma admitted for series evaluation before Y selective internal radiotherapy (SIRT). Intra-arterial hepatic Tc macroaggregated albumin scan before Y-SIRT revealed a 2.7-cm incidental low-density thyroid nodule with hot uptake. TcO4 scan revealed corresponding hot uptake in the thyroid nodule with near background uptake of normal thyroid tissue, favored autonomous nodule. After Y-microsphere SIRT, bremstrallung imaging revealed no Y-microsphere deposition to thyroid.
Palliative procedures in patients with advanced lung cancer: Analysis from a prospective outcomes database
Authors: T. J. Miner, J. Gaydos-Gabriel, D. P. Jaques
Journal: Journal of Clinical Oncology (2006)

8606 Background: Decisions regarding the appropriate use of palliative procedures continue to challenge those who care for patients with advanced cancer. This study examines the outcomes of palliative procedures performed for lung cancer compared to other primary malignancies. Methods: Procedures to explicitly palliate symptoms of advanced cancer were identified prospectively. Patients were observed for &gt;90 days or until death. Clinical outcomes were evaluated based on the type of primary malignancy. Results: There were 1,022 palliative procedures performed in 823 patients from July 2002 to June 2003. Palliative procedures were most commonly performed in patients with lung cancer (14%, 117/823) for neurologic symtpoms-39%, shortness of breath-29%, gastrointestinal obstruction-15%, and other symtpoms-17%. Symptom improvement or resolution within 30 days was less common in patients with lung cancer (66%, 77/117) than in those with other primary malignancies (82%, 579/706, p=0.02). As observed in other cancers, recurrence of the primary symptom occurred in 25% (p=0.46) while treatment of debilitating additional symptoms was required in 30% (p=0.39). Palliative procedures in patients with lung cancer were associated with similar 30-day postoperative morbidity (33% versus 34%, p=0.97) but increased mortality (22% versus 10%, p&lt;0.001). Median overall survival from the time of the palliative procedure was significantly shorter in patients with lung cancer than all other primary malignancies (90 days versus 124 days, p&lt;0.001). Conclusions: Careful patient selection for palliative procedures is required in patients with advanced lung cancer. These interventions are associated with shorter anticipated survival, higher perioperative mortality and less frequent symptom resolution compared to palliative procedures performed in patients with other primary malignancies. Symptom severity may necessitate, however, palliative procedures in patients with lung cancer. The compelling nature of shortness of breath often dictates intervention regardless of durability and illustrates the importance of symptom relief for a significant percentage of remaining life even when measured in days. No significant financial relationships to disclose.