tbuckley/cabot-search huggingface dataset:
Enhanced transdermal delivery of meloxicam by nanocrystals: Preparation, in vitro and in vivo evaluation
Authors: Qin Yu, Xiying Wu, Quangang Zhu, Wei Wu, Zhongjian Chen, Ye Li, Yi Lu
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Meloxicam (MLX) is efficient in relieving pain and inflammatory symptoms, which, however, is limited by the poor solubility and gastrointestinal side effects. The objective of this study is to develop a nanocrystal formulation to enhance transdermal delivery of MLX. MLX nanocrystals were successfully prepared by the nanoprecipitation technique based on acid-base neutralization. With poloxamer 407 and Tween 80 (80/20, w/w) as mixed stabilizers, MLX nanocrystals with particle size of 175 nm were obtained. The crystalline structure of MLX nanocrystals was confirmed by both differential scanning calorimetry and X-ray powder diffractometry. However, the nanoprecipitation process reduced the crystallinity of MLX. Nanocrystals increased both in vitro and in vivo transdermal permeation of MLX compared with the solution and suspension counterparts. Due to the enhanced apparent solubility and dissolution as well as the facilitated hair follicular penetration, nanocrystals present a high and prolonged plasma MLX concentration. And 2.58- and 4.4-fold increase in AUC0→24h was achieved by nanocrystals comparing with solution and suspension, respectively. In conclusion, nanocrystal is advantageous for transdermal delivery of MLX.
Isotype-specific agglutination-PCR (ISAP): A sensitive and multiplex method for measuring allergen-specific IgE
Authors: Cheng-ting Tsai, Kaori Mukai, Peter V. Robinson, Melissa A. Gray, Malika B. Waschmann, Shu-Chen Lyu, Mindy Tsai, Rebecca S. Chinthrajah, Kari C. Nadeau, Carolyn R. Bertozzi, Stephen J. Galli
Journal: Journal of Allergy and Clinical Immunology (2017)
Changes in regulatory B-cell levels in bone marrow, blood, and sputum of patients with asthma following inhaled allergen challenge
Authors: John-Paul Oliveria, Amani I. El-Gammal, Michelle Yee, Caitlin D. Obminski, Tara X. Scime, Richard M. Watson, Karen Howie, Paul M. O'Byrne, Roma Sehmi, Gail M. Gauvreau
Journal: Journal of Allergy and Clinical Immunology (2017)
A nomogram associated with high probability of invasive carcinoma on the surgical specimen in patients with preoperative diagnosis of ductal carcinoma in situ of the breast.
Authors: Takafumi Kondo, Naoki Hayashi, Sachiko Ohde, Hiroshi Yagata, Atsushi Yoshida, Seigo Nakamura, Koyu Suzuki, Hiroko Tsunoda, Hideko Yamauchi
Journal: Journal of Clinical Oncology (2014)

1595 Background: Sentinel node biopsy is frequently performed for patients with preoperative diagnosis of ductal carcinoma in situ (DCIS) by needle biopsy because of a possibility of postoperative diagnose of invasive ductal carcinoma (IDC) on the surgical specimen. Inessential sentinel node biopsy would be omitted, if final postoperative diagnosis could be predicted DCIS accurately. The aim of this study are to determine clinicopathological factors associated with postoperative diagnosis of IDC regardless of preoperative diagnosis of DCIS, and to conduct a model to predict IDC on surgical specimen. Methods: Pre- and postoperative pathological diagnosis and radiological findings on 1,251 consecutive patients who were diagnosed DCIS by preoperative core needle biopsy (CNB) or vacuum-assisted breast biopsy and underwent surgical resection from 2003 to 2012 were retrospectively assessed. Multivariate logistic regression was applied to generate the nomogram to predict IDC. Results: Of the 1,251 patients, 318 (25.4%) were diagnosed IDC on surgical specimen. On multivariate analysis, no evidence of sclerosing adenosis on preoperative biopsy specimen (odds ratio (OR) 0.46, 95%CI 0.25-0.85, p = 0.013), pleomorphic calcifications on mammogram (OR 1.68, 95%CI 1.14-2.47, p = 0.009), suspicious of invasive carcinoma on ultrasound and/or MRI (OR 2.13, 95%CI 1.51-3.00, p = 0.000), tumor size≧2cm on ultrasound (OR 1.80, 95%CI 1.05-3.06, p = 0.032) were independent predictive factors. HER2-positive (OR 1.54, 95%CI 0.98-2.41, p = 0.062) and comedo necrosis (OR 1.42, 95%CI 0.99-2.03, p = 0.056) were also same trend. A nomogram using these factors predicted the correlation with AUC of 0.67 (95% CI 0.63-0.71). Conclusions: Our nomogram showed the correlation of the presence of invasive breast carcinoma on surgical specimen regardless of preoperative diagnosis of DCIS. Prospective external validation is needed before being implemented in clinical practice.
Abstract 20347: Kidney Transplantation in a Patient Lacking Cytosolic Phospholipase A2 Leads to Urinary Prostacyclin and Thromboxane A2 Metabolites Within Normal Ranges
Authors: Jane A Mitchell, Rebecca Knowles, Nicholas S Kirkby, Daniel M Reed, William White, Matthew L Edin, Hilary Longhurst, Magdi Yaqoob, Ginger L Milne, Darryl C Zeldin, Timothy D Warner
Journal: Circulation (2016)

Measurements of metabolites of prostacyclin and thromboxane A2 (TXA2) in the urine have been held as the best estimates of eicosanoid production in the circulation. As such, measurement of these ur...
Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma
Authors: Steven M. Horwitz, Raphael Koch, Pierluigi Porcu, Yasuhiro Oki, Alison Moskowitz, Megan Perez, Patricia Myskowski, Adam Officer, Jacob D. Jaffe, Sara N. Morrow, Kerstin Allen, Mark Douglas, Howard Stern, Jennifer Sweeney, Patrick Kelly, Virginia Kelly, Jon C. Aster, David Weaver, Francine M. Foss, David M. Weinstock
Journal: Blood (2017)
An Implementation Guide to Reducing Overtreatment of Asymptomatic Bacteriuria
Authors: Michael Daniel, Sara Keller, Mohammad Mozafarihashjin, Amit Pahwa, Christine Soong
Journal: JAMA Internal Medicine (2017)

Treatment of asymptomatic bacteriuria (ASB) frequently lacks appropriate indication, yet remains prevalent across settings. Numerous guidelines, professional societies, and campaigns such as Choosing Wisely advocate against this low-value practice. Efforts aimed at reducing unnecessary treatment of ASB demonstrate improved costs, and avoidable harm without increased risk of adverse events. We propose an evidence-based implementation guide to aid practitioners in reducing inappropriate treatment of ASB.
Potassium channels in melanoma cells are functionally upregulated by chronic hypoxia
Authors: Kristina M. Schoenherr, Nobuyoshi Tajima, Martin Kaatz, Stefan H. Heinemann, Roland Schoenherr
Journal: Cancer Research (2005)

5234   Potassium channels are known to control neuronal excitability and to contribute to membrane resting potentials. In the past few years, increasing evidence emerged for an additional and unexpected role in oncogenesis. Potassium channel expression has been confirmed for a variety of tumors from different histologic origins including melanoma, and channel blockade can reduce proliferation rates in cell cultures. We previously found that the potassium channel repertoire of the human melanoma cell line IGR1 is restricted to voltage-gated  ether-a-go-go  channels (EAG1) and calcium-activated potassium channels of the IK/SK type. We now provide first evidence for the expression of these channels in acutely isolated primary cell cultures from melanoma metastases. Quantitative RT-PCR, as well as patch-clamp measurements confirmed the expression of EAG1 and IK/SK channels in melanoma cells from different patients, but with individual patterns. As reduced oxygen supply is a common feature in many tumors including melanoma, we addressed the question how these potassium channels are influenced by chronic hypoxia (3% oxygen). Interestingly, in IGR1 cells both channel types showed a 2-3 fold increase in current amplitude under hypoxic growth conditions. A comparable channel upregulation was also observed in individual, but not in all cell cultures from patient material. Under hypoxic conditions, IGR1 cells as well as individual primary cultures showed increased proliferation rates, as measured by BrdU incorporation. We used IGR1 cells to study the potential mechanisms underlying the observed hypoxia regulation of potassium channels. Overexpression of the hypoxia-inducible transcription factor HIF-1α induced functional upregulation of IK/SK channels, while overexpression of the von Hippel-Lindau tumor suppressor protein (pVHL) had the opposite effect. In contrast, EAG currents were not responsive to HIF-1α but could be downregulated by pVHL. Thus, at least IK/SK channels are closely linked to the main oxygen sensor HIF-1α, a key regulator of tumor progression, and to the tumor suppressor protein pVHL. It is known that tumor hypoxia correlates with poor prognosis in melanoma. Based on our findings in IGR1 cells and cultures from patient biopsies, we propose that upregulation of potassium channels provides a new mechanism supporting the hypoxic progression of tumor cells in melanoma.
Effectiveness of low-level laser therapy in lichen planopilaris
Authors: Pablo Fonda-Pascual, Oscar M. Moreno-Arrones, David Saceda-Corralo, Ana R. Rodrigues-Barata, Cristina Pindado-Ortega, Pablo Boixeda, Sergio Vaño-Galvan
Journal: Journal of the American Academy of Dermatology (2017)
Divergent Connectivity of Homologous Command-like Neurons Mediates Segment-Specific Touch Responses in Drosophila
Authors: Suguru Takagi, Benjamin Thomas Cocanougher, Sawako Niki, Dohjin Miyamoto, Hiroshi Kohsaka, Hokto Kazama, Richard Doty Fetter, James William Truman, Marta Zlatic, Albert Cardona, Akinao Nose
Journal: Neuron (2017)
Clinical Translation of Mesenchymal Stromal Cell Therapies in Nephrology
Authors: Norberto Perico, Federica Casiraghi, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2017)

Mesenchymal stromal cells have emerged as potential candidates for cell-based therapies to modulate the immune response in organ transplantation and repair tissues after acute or chronic injury. Preclinical studies have shown convincingly in rodent models that mesenchymal stromal cells can prolong solid organ graft survival and that they can induce immune tolerance, accelerate recovery from AKI, and promote functional improvement in chronic nephropathies. Multiple complex properties of the cells, including immunomodulatory, anti-inflammatory, and proregenerative effects, seem to contribute. The promising preclinical studies have encouraged investigators to explore the safety, tolerability, and efficacy of mesenchymal stromal cell-based therapy in pilot clinical trials, including those for bone marrow and solid organ transplantation, autoimmune diseases, and tissue and organ repair. Here, we review the available data on culture-expanded mesenchymal stromal cells tested in renal transplantation, AKI, and CKD. We also briefly discuss the relevant issues that must be addressed to ensure rigorous assessment of the safety and efficacy of mesenchymal stromal cell therapies to allow the translation of this research into the practice of clinical nephrology.
Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy
Authors: Nicolas Diguet, Samuel A.J. Trammell, Cynthia Tannous, Robin Deloux, Jérôme Piquereau, Nathalie Mougenot, Anne Gouge, Mélanie Gressette, Boris Manoury, Jocelyne Blanc, Marie Breton, Jean-François Decaux, Gareth G. Lavery, István Baczkó, Joffrey Zoll, Anne Garnier, Zhenlin Li, Charles Brenner, Mathias Mericskay
Journal: Circulation (2017)

Background: Myocardial metabolic impairment is a major feature in chronic heart failure. As the major coenzyme in fuel oxidation and oxidative phosphorylation and a substrate for enzymes signaling energy stress and oxidative stress response, nicotinamide adenine dinucleotide (NAD + ) is emerging as a metabolic target in a number of diseases including heart failure. Little is known on the mechanisms regulating homeostasis of NAD + in the failing heart. Methods: To explore possible alterations of NAD + homeostasis in the failing heart, we quantified the expression of NAD + biosynthetic enzymes in the human failing heart and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by Serum Response Factor transcription factor depletion in the heart (SRF HKO ) or of cardiac hypertrophy triggered by transverse aorta constriction. We studied the impact of NAD + precursor supplementation on cardiac function in both mouse models. Results: We observed a 30% loss in levels of NAD + in the murine failing heart of both DCM and transverse aorta constriction mice that was accompanied by a decrease in expression of the nicotinamide phosphoribosyltransferase enzyme that recycles the nicotinamide precursor, whereas the nicotinamide riboside kinase 2 (NMRK2) that phosphorylates the nicotinamide riboside precursor is increased, to a higher level in the DCM (40-fold) than in transverse aorta constriction (4-fold). This shift was also observed in human failing heart biopsies in comparison with nonfailing controls. We show that the Nmrk2 gene is an AMP-activated protein kinase and peroxisome proliferator-activated receptor α responsive gene that is activated by energy stress and NAD + depletion in isolated rat cardiomyocytes. Nicotinamide riboside efficiently rescues NAD + synthesis in response to FK866-mediated inhibition of nicotinamide phosphoribosyltransferase and stimulates glycolysis in cardiomyocytes. Accordingly, we show that nicotinamide riboside supplementation in food attenuates the development of heart failure in mice, more robustly in DCM, and partially after transverse aorta constriction, by stabilizing myocardial NAD + levels in the failing heart. Nicotinamide riboside treatment also robustly increases the myocardial levels of 3 metabolites, nicotinic acid adenine dinucleotide, methylnicotinamide, and N1-methyl-4-pyridone-5-carboxamide, that can be used as validation biomarkers for the treatment. Conclusions: The data show that nicotinamide riboside, the most energy-efficient among NAD precursors, could be useful for treatment of heart failure, notably in the context of DCM, a disease with few therapeutic options.
Abstract B34: Investigating disruptions in the circadian clock in cancer cells
Authors: Waldo Lexow, Sian-Ailin Da Silva, Virna D. Leaner, Pauline J. van der Watt
Journal: Cancer Research (2017)

Abstract The circadian clock is man's internal time-keeping mechanism; it synchronizes human physiology with the external cycle of day and night. At the molecular level, all cells display a circadian clock driven by core clock proteins that constitute transcription-translation feedback loops, generating oscillating patterns of circadian clock gene expression over time. It is becoming increasingly apparent that disruptions in the circadian clock may contribute to cancer development. This study aimed to investigate the molecular components of the circadian clock in two cancer types prevalent in South Africa: cervical and oesophageal cancer. To our knowledge the circadian clock has not previously been investigated in these cancer types. Microarray and real-time RT-PCR analyses revealed significantly decreased expression of Period 2 (Per2) mRNA in cervical and oesophageal cancer patient tissue compared to normal tissue. Cervical and oesophageal cancer cell lines similarly displayed significantly reduced mRNA and protein levels of certain circadian clock genes, including positive and negative regulators of the circadian clock. Nuclear transport of circadian clock proteins was investigated, since cancer cells display increased nuclear transport rates and circadian clock proteins rely on nucleocytoplasmic shuttling to maintain the correct pace of the circadian clock. Fluorescence recovery after photobleaching (FRAP) analysis was performed and revealed increased nuclear import rates of Bmal1 in cancer compared to normal cells. Altered expression and nuclear import rates of circadian clock proteins in cancer cells suggest these cells might harbor an impaired circadian clock. Luminescence assays are thus currently being employed to determine whether cancer cells display rhythmic expression of core clock genes, as an indication of a functioning circadian clock. A real-time bioluminescence imager is being used to measure Bmal1 and Per2 promoter-luciferase activities in cancer cells over time, after synchronization of circadian oscillators with the glucocorticoid analogue, Dexamethasone. This type of study is relevant to the field of chronotherapy, where elucidating differences in circadian clock functioning in normal and cancer cells could yield better insights into the timing of administration of chemotherapy, ultimately ensuring a better patient response. Citation Format: Waldo Lexow, Sian-Ailin Da Silva, Virna D. Leaner, Pauline J. van der Watt. Investigating disruptions in the circadian clock in cancer cells [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B34.
Predictive Performance of Four Programmed Cell Death Ligand 1 Assay Systems on Nivolumab Response in Previously Treated Patients with Non–Small Cell Lung Cancer
Authors: Daichi Fujimoto, Yuki Sato, Keiichiro Uehara, Kaori Ishida, Junya Fukuoka, Takeshi Morimoto, Hayato Kawachi, Ryobu Mori, Munehiro Ito, Shunsuke Teraoka, Kazuma Nagata, Atsushi Nakagawa, Kojiro Otsuka, Yukihiro Imai, Keisuke Tomii
Journal: Journal of Thoracic Oncology (2017)
Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy
Authors: Hanqiu Zheng, Yangjin Bae, Sabine Kasimir-Bauer, Rebecca Tang, Jin Chen, Guangwen Ren, Min Yuan, Mark Esposito, Wenyang Li, Yong Wei, Minhong Shen, Lanjing Zhang, Nikolai Tupitsyn, Klaus Pantel, Chadwick King, Jan Sun, Jodi Moriguchi, Helen Toni Jun, Angela Coxon, Brendan Lee, Yibin Kang
Journal: Cancer Cell (2017)
STAT5BN642H is a driver mutation for T cell neoplasia
Authors: Ha Thi Thanh Pham, Barbara Maurer, Michaela Prchal-Murphy, Reinhard Grausenburger, Eva Grundschober, Tahereh Javaheri, Harini Nivarthi, Auke Boersma, Thomas Kolbe, Mohamed Elabd, Florian Halbritter, Jan Pencik, Zahra Kazemi, Florian Grebien, Markus Hengstschläger, Lukas Kenner, Stefan Kubicek, Matthias Farlik, Christoph Bock, Peter Valent, Mathias Müller, Thomas Rülicke, Veronika Sexl, Richard Moriggl
Journal: Journal of Clinical Investigation (2017)

STAT5B is often mutated in hematopoietic malignancies. The most frequent STAT5B mutation, Asp642His (N642H), has been found in over 90 leukemia and lymphoma patients. Here, we used the Vav1 promoter to generate transgenic mouse models that expressed either human STAT5B or STAT5BN642H in the hematopoietic compartment. While STAT5B-expressing mice lacked a hematopoietic phenotype, the STAT5BN642H-expressing mice rapidly developed T cell neoplasms. Neoplasia manifested as transplantable CD8+ lymphoma or leukemia, indicating that the STAT5BN642H mutation drives cancer development. Persistent and enhanced levels of STAT5BN642H tyrosine phosphorylation in transformed CD8+ T cells led to profound changes in gene expression that were accompanied by alterations in DNA methylation at potential histone methyltransferase EZH2-binding sites. Aurora kinase genes were enriched in STAT5BN642H-expressing CD8+ T cells, which were exquisitely sensitive to JAK and Aurora kinase inhibitors. Together, our data suggest that JAK and Aurora kinase inhibitors should be further explored as potential therapeutics for lymphoma and leukemia patients with the STAT5BN642H mutation who respond poorly to conventional chemotherapy.
Burkholderia stabilis outbreak associated with contaminated commercially-available washing gloves, Switzerland, May 2015 to August 2016
Authors: Rami Sommerstein, Urs Führer, Elia Lo Priore, Carlo Casanova, Dominik M Meinel, Helena MB Seth-Smith, Andreas Kronenberg, Daniel Koch, Laurence Senn, Andreas F Widmer, Adrian Egli, Jonas Marschall
Journal: Eurosurveillance (2017)

We describe an outbreak of Burkholderia stabilis associated with contaminated washing gloves, a commercially available Class I medical device. Triggered by an increase in Burkholderia cepacia complex (BCC) bacteremias and the detection of BCC in unopened packages of washing gloves, an ad hoc national outbreak committee comprising representatives of a public health organisation, a regulatory agency, and an expert association convened and commissioned an outbreak investigation. The investigation included retrospective case finding across Switzerland and whole genome sequencing (WGS) of isolates from cases and gloves. The investigation revealed that BCC were detected in clinical samples of 46 cases aged 17 to 91 years (33% females) from nine institutions between May 2015 and August 2016. Twenty-two isolates from case patients and 16 from washing gloves underwent WGS. All available outbreak isolates clustered within a span of < 19 differing alleles, while 13 unrelated clinical isolates differed by > 1,500 alleles. This BCC outbreak was rapidly identified, communicated, investigated and halted by an ad hoc collaboration of multiple stakeholders. WGS served as useful tool for confirming the source of the outbreak. This outbreak also highlights current regulatory limitations regarding Class I medical devices and the usefulness of a nationally coordinated outbreak response.
Epidemiología de la meningitis meningocócica y modificaciones del sistema de vigilancia en Polonia, 1970-2006
Authors: O Gryniewicz, J Kolbusz, M Rosinska, A Zielinski, P Stefanoff
Journal: Eurosurveillance (2007)

El objetivo de este estudio era describir las caracteristicas generales de la epidemiologia de la meningitis meningococica en 1970-2006 en Polonia, en el contexto de las modificaciones efectuadas en los metodos del sistema de vigilancia.
Antisense oligonucleotides offer hope to patients with Charcot-Marie-Tooth disease type 1A
Authors: Michael E. Shy
Journal: Journal of Clinical Investigation (2017)

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common heritable peripheral neuropathy and results from a duplication on chromosome 17 that results in an extra copy and increased dosage of peripheral myelin protein 22 (PMP22). Zhao et al., in this issue of the JCI, successfully utilized antisense oligonucleotides (ASOs) to reduce PMP22 and ameliorated neuropathy in both mouse and rat models of CMT1A. These data confirm that strategies to reduce PMP22 have potential as effective therapeutic approaches for CMT1A and lay the groundwork for clinical trials in humans afflicted with this chronic, debilitating neurodegenerative disease.