tbuckley/cabot-search huggingface dataset:
Abstract 16117: Nonresponders to Cardiac Rehabilitation and Outcomes
Authors: Alban De Schutter, Carl Lavie, Eiman Jahangir, Arthur Menezes, Homeyar Dinshaw, Kelly Shum, Ross Arena, Richard Milani
Journal: Circulation (2015)

Introduction: Studies of coronary heart disease (CHD) and cardiac rehabilitation (CR) have traditionally focused on increasing enrollment in CR. We examine here the prognosis of patients who enrolled and completed CR, but saw no significant improvement in exercise capacity [nonresponders (NR)]. Hypothesis: Nonresponders have a poor prognosis. Methods: 780 CHD patients who completed CR with cardiopulmonary exercise testing (CPX) before and after the intervention were divided according to improvement in exercise tolerance (ET; no change or decline vs improvement in metabolic equivalent). Mortality was tracked post CR for all patients; 1 to 161 months of follow-up (mean 6.4 years). Results: 243 (31%) subjects were NR. After adjustment for body mass index, age, gender, ejection fraction and baseline ET, lack of improvement in exercise capacity was associated with a statistically significant 55% increase in mortality (p=0.03; Figure 1). Higher age (OR 1.02; p 0.05) and baseline ET (OR 1.07; p 0.001) was significantly associated with being a NR, but depression, gender and ejection fraction were not significant risk factors. Conclusions: A substantial proportion of subjects referred to CR have no improvement in ET and comparatively demonstrate a poor prognosis. Further investigation into the identifying characteristics of this population is needed to examine if their prognosis can be altered.
TCT-389 Does well-developed coronary collateral circulation have an influence on myocardial viability in late presentation myocardial infarction?
Authors: Alejandro Gutierrez-Barrios, Dolores Cañadas, Enrique Diaz-Retamino, German Calle Perez, Rafael Vázquez-García
Journal: Journal of the American College of Cardiology (2017)
Oral epithelial cells orchestrate innate type 17 responses to <i>Candida albicans</i> through the virulence factor candidalysin
Authors: Akash H. Verma, Jonathan P. Richardson, Chunsheng Zhou, Bianca M. Coleman, David L. Moyes, Jemima Ho, Anna R. Huppler, Kritika Ramani, Mandy J. McGeachy, Ilgiz A. Mufazalov, Ari Waisman, Lawrence P. Kane, Partha S. Biswas, Bernhard Hube, Julian R. Naglik, Sarah L. Gaffen
Journal: Science Immunology (2017)

Candidalysin, a hypha-associated fungal peptide, drives interleukin-17 responses to Candida albicans .
Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2
Authors: George S. Sheppard, Jieyi Wang, Megumi Kawai, Gary T. Wang, Steve D. Fidanze, William J. Sanders, Nwe Y. Bamaung, Scott A. Erickson, Robert A. Mantei, Fabio Palazzo, David M. Barnes, Jason S. Tedrow, Lawrence Kolaczkowski, Anil Vasudevan, David C. Park, Douglas M. Kalvin, Lora Tucker-Garcia, Pingping Luo, Qian Zhang, Chang H. Park, Ki H. Kim, Andrew Petros, Edward Olejniczak, David Nettesheim, Phillip Hajduk
Journal: Cancer Research (2005)

2531   Methionine aminopeptidase-2 (MetAP2), an intracellular enzyme responsible for the removal of the N-terminal initiator methionine from nascent proteins, has been suggested as a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 was identified by ASMS screening. These micromolar hits, typified by A-193400 (MetAP2 IC 50  = 13 μM) and A-444148 (MetAP2 IC 50  = 1.3 μM) were rapidly improved to nanomolar leads based on insights from protein crystallography. Compounds with good enzyme inhibitory activity and promising oral bioavailability in mice such as A-751277 (MetAP2 IC 50  = 0.010 μM, F = 93%) were obtained; however the compounds displayed extensive binding to HSA and had limited activity in cellular assays (EC 50  = 0.40 μM for HMVEC proliferation, EC 50  = 2.1 μM for HT-1080 proliferation). Modifications based on structural information on the binding of lead compounds to domain 3 of albumin allowed the identification of compounds with significant improvements in both parameters such as A-832234 (MetAP2 IC 50  = 0.011 μM, HMVEC EC 50  = 0.007 μM, HT-1080 EC 50  = 0.006 μM) and A-847519 (MetAP2 IC 50  = 0.017 μM, HT-1080 EC 50  = 0.036 μM) which show good cellular activity in both proliferation and methionine processing assays.
TCT-283 Comparison of Transcatheter Mitral Valve Repair vs. Surgical Mitral Valve Repair in Patients with Advanced Kidney Disease: Insights from The National (Nationwide) Inpatient Sample (NIS)
Authors: Rajkumar Doshi, Pratik Agrawal, Jay Shah, Tapan Miyani, Dhaval Patel, Perwaiz Meraj
Journal: Journal of the American College of Cardiology (2017)
Interdisciplinary Disease-Based Peer Review
Authors: Michael Nurok, Bruce Gewertz
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Formas clássicas e emergentes de botulismo: a situação actual em Itália
Authors: P Aureli, L Fenica, G Franciosa
Journal: Eurosurveillance (1999)

O botulismo e uma doenca neuroparalisante, rara e grave. Em humanos, estao descritas quatro formas de botulismo: botulismo alimentar, o mais recentemente descrito botulismo de origem em feridas, botulismo infantil e botulismo ‘semelhante ao infantil’. As duas ultimas formas sao por vezes agrupadas sob o termo ‘botulismo com toxemia intestinal’, para descrever a infeccao intestinal por clostridios neurotoxigenicos em criancas e adultos. Ate agora, foram associadas as quatro formas de botulismo no homem, tres especies de Clostridium: o classico C. botulinum que produz toxinas dos tipos A, B, E e F, e duas estirpes raras de C. butyricum e C. baratii, que produzem toxinas semelhantes as toxinas dos tipos E e F do C. botulinum, respectivamente. Ambas as formas classica e emergente ocorreram em Italia.
Cytoreduction and androgen signaling modulation by abiraterone acetate (AA) plus leuprolide acetate (LHRHa) versus LHRHa in localized high-risk prostate cancer (PCa): Preliminary results of a randomized preoperative study.
Authors: Eleni Efstathiou, John W. Davis, Patricia Troncoso, Mark Anton Titus, Anh Hoang, Sijin Wen, Amado J. Zurita, Namphuong Tran, Arturo Molina, Christopher Logothetis
Journal: Journal of Clinical Oncology (2012)

4556 Background: Endocrine to “intracrine” androgen signaling transition, a milestone in the lethal progression of PCa, has not been characterized in localized high risk disease. Signaling heterogeneity under the selective pressure of castration may account for response differences. Methods: A single institution preoperative study of 12 weeks AA 1g/prednisone 5 mg + LHRHa compared to LHRHa (randomized 2:1) was conducted in patients (pts) with high risk PCa (clinical stage ≥T1c and biopsy Gleason score ≥8, or ≥T2b, Gleason ≥ 7 and PSA &gt; 10ng/ml). Primary aim: Assess difference in down staging (≤ ypT2) and safety. Secondary aims: Assess difference in androgen biosynthesis, androgen signaling (AR, AR variants, NKX 3.1, ERG, PSA) proliferation apoptosis and candidate treatment resistance pathways. Results: We report on 37 (50 enrolled) pts who had prostatectomy. AA+LHRHa was given to 25pts, LHRHa to 12. Median age is 61 ys (46-74). Preoperative PSA was &lt;0.1ng/ml in 17/25 (68%) AA+LHRHa vs 0/12 LHRHa (p 0.0001). ypT2N0 occurred in 15/25 (60%) AA+LHRHa treated pts vs 4/12 (33%) LHRHa (p 0.17). Near complete cytoreduction (&lt;6mm scattered cells) occurred in 6/25 (24%) AA+LHRHa vs 1/12 (8%) LHRHa. Lymph node infiltration in 7/25 (28%) AA+LHRHa vs 6/12 (50%) LHRHa. Margin positivity in 2/25 (8%) AA+LHRHa vs 4/12 (33%) LHRHa (p 0.07). Grade 3 AA related AEs: elevated AST/ALT 4 (discontinued AA), hypertension 3. One AA+LHRHa pt had postop pulmonary embolism. Androgen signaling and proliferation suppression is more profound in AA+LHRHa treated remaining tumor cells (Table). Conclusions: Addition of AA to LHRHa results in greater cytoreduction, suppression of PSA and androgen signaling compared to LHRHa in high risk PCa. Findings support the hypothesis that intracrine androgen signaling is a therapy target in patients with untreated PCa and form the foundation for a marker driven treatment strategy. [Table: see text]
Outgrowing the laboratory diagnosis of type 1 von <scp>W</scp>illebrand disease: A two decade study
Authors: Mouhamed Yazan Abou‐Ismail, Gbolahan O. Ogunbayo, Michelle Secic, Peter A. Kouides
Journal: American Journal of Hematology (2017)

Von Willebrand Factor (VWF) levels are known to increase with age in the general population, but that effect is unclear in von Willebrand disease (VWD) patients. Thus, it is important to assess the trends of VWF levels with age, and the extent and rate of their normalization in patients with VWD. In a retrospective cohort study, we reviewed the medical records of 126 patients between 1996 and 2016 who met the NHLBI diagnostic criteria for type 1 VWD or "Low VWF" (LVWF). We followed all their historically documented VWF antigen (VWF:Ag), VWF activity (VWF:RCo), and Factor VIII (FVIII) levels longitudinally over time, correlating data with clinical setting at time of testing. The average duration of follow-up was 10.5 ± 3.7 years (SD). Out of the total study population, 27.8% achieved the primary outcome of complete normalization (CN) of both VWF:Ag and VWF:RCo levels, including 19.6% and 32.5% of those with VWD and LVWF, respectively. Linear regression demonstrated statistically significant positive trends of VWF:Ag, VWF:RCo, FVIII with time, calculated at 2.4, 1.4, and 1.4 U dL-1/year, respectively (P < .001 each). In the largest study population of VWD patients to date whose levels were followed longitudinally, there is a statistically significant rise in VWF:Ag, VWF:RCo, and FVIII levels observed with time. CN of both VWF:Ag and VWF:RCo levels was observed in almost a third of patients with VWD or LVWF, over an average of 10 years. Whether the bleeding phenotype also improves is unclear and requires further study.
TCT-658 Ischaemic postconditioning reduces the extent of myocardial necrosis and microvascular obstruction zone in acute ST-elevation myocardial infarction
Authors: Aleksander Araszkiewicz, Marek Grygier, Malgorzata Pyda, Justyna Rajewska-Tabor, Maciej Lesiak, Stefan Grajek
Journal: Journal of the American College of Cardiology (2017)
PS06.02 Drug-Tolerant EGFR Mutant Lung Cancer Cells Rely on MCL-1 Translation and are Eliminated by MCL-1 Inhibitors
Authors: K. Song, T.L. Lochmann, N.U. Patel, J. Ham, B.E. Windle, H. Harada, J.D. Leverson, A.J. Souers, H. Ebi, A.C. Faber
Journal: Journal of Thoracic Oncology (2017)
Cockroach is a major cross‐reactive allergen source in shrimp‐sensitized rural children in southern China
Authors: Z. Yang, J. Zhao, N. Wei, M. Feng, M. Xian, X. Shi, Z. Zheng, Q. Su, G. W. K. Wong, J. Li
Journal: Allergy (2017)

Abstract Background Little is known about the prevalence of food allergy ( FA ) in China. The aim of this study was to investigate the disparity of FA between urban and rural areas in southern China. Methods EuroPrevall questionnaire responses were obtained from 5542 school‐age children in urban Guangzhou and 5319 in rural Shaoguan. A case‐control study enrolled 190 children with adverse reactions ( AR s) after food intake as cases and 212 controls in Guangzhou, whereas 116 cases and 233 controls in Shaoguan. These subjects underwent skin prick test ( SPT ) and serum IgE measurements to food and inhalant allergens. Allergen extracts from shrimp, house dust mite ( HDM ), and cockroach were prepared for IgE cross‐reactivity testing in 23 Guangzhou and 20 Shaoguan shrimp‐sensitized subjects. Results The prevalence of AR s to shrimp was higher in Guangzhou than in Shaoguan children (3.5% vs 1.4%, P &lt; .001). However, sensitization rate to shrimp ( SPT : 3.7% vs 11.2%, P = .015; IgE: 12.6% vs 36.2%, P &lt; .001) and cockroach ( SPT : 5.3% vs 33.5%; IgE: 2.6% vs 27.6%, P &lt; .001) was lower in Guangzhou. A significant correlation between shrimp and HDM /cockroach IgE was found in Shaoguan children. The proportions of positive IgE to tropomyosin (Pen a 1, Der p 10) were lower than 7.4% in both areas. Cockroach allergen has a significantly higher inhibition rate of binding to IgE to house dust mite allergens in Shaoguan sera. Conclusion Shrimp is a common allergic food in southern China. Higher proportion of shrimp sensitization in rural subjects could be explained by cross‐reactivity to cockroach. Tropomyosin was not a major allergen responding to the cross‐reactivity.
Mild Traumatic Brain Injury and Mental Health—Reply
Authors: Christine L. Mac Donald, Jesse R. Fann, Nancy R. Temkin
Journal: JAMA Neurology (2017)

In Reply We appreciate the interest of Smith and Vipler in our study.1 The 2 internal medicine physicians raise 3 concerns regarding our findings about the prevalence of comorbid mental health conditions among service members following a concussive blast injury.
EMC3 coordinates surfactant protein and lipid homeostasis required for respiration
Authors: Xiaofang Tang, John M. Snowball, Yan Xu, Cheng-Lun Na, Timothy E. Weaver, Geremy Clair, Jennifer E. Kyle, Erika M. Zink, Charles Ansong, Wei Wei, Meina Huang, Xinhua Lin, Jeffrey A. Whitsett
Journal: Journal of Clinical Investigation (2017)

Adaptation to respiration at birth depends upon the synthesis of pulmonary surfactant, a lipid-protein complex that reduces surface tension at the air-liquid interface in the alveoli and prevents lung collapse during the ventilatory cycle. Herein, we demonstrated that the gene encoding a subunit of the endoplasmic reticulum membrane complex, EMC3, also known as TMEM111 (Emc3/Tmem111), was required for murine pulmonary surfactant synthesis and lung function at birth. Conditional deletion of Emc3 in murine embryonic lung epithelial cells disrupted the synthesis and packaging of surfactant lipids and proteins, impaired the formation of lamellar bodies, and induced the unfolded protein response in alveolar type 2 (AT2) cells. EMC3 was essential for the processing and routing of surfactant proteins, SP-B and SP-C, and the biogenesis of the phospholipid transport protein ABCA3. Transcriptomic, lipidomic, and proteomic analyses demonstrated that EMC3 coordinates the assembly of lipids and proteins in AT2 cells that is necessary for surfactant synthesis and function at birth.
Patients with low risk of developing glaucoma should not be referred to specialist care, says NICE
Authors: Anne Gulland
Journal: BMJ (2017)

Patients with risk factors for glaucoma should only be referred to specialist care when their inner eye pressure reaches 24 mm Hg, according to a new guideline from the National Institute of Health and Care Excellence (NICE).1

The new guideline says that patients with increased ocular hypertension, a major risk factor for chronic open angle glaucoma (COAG), should only be referred to specialist care when the pressure reaches 24 mm Hg. This is a …
TCT-178 Everolimus-Eluting Stents versus Coronary Artery Bypass Graft Surgery for Left Main Coronary Artery Disease in Patients with and without Chronic Kidney Disease
Authors: Gennaro Giustino, Joseph Sabik, Bjorn Redfors, Milan Milojevic, Patrick Serruys, David Kandzari, Marie-Claude Morice, Anthony Gershlick, Philippe Genereux, Ovidiu Dressler, Zixuan Zhang, Roxana Mehran, A. Pieter Kappetein, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
Reply to Giulia I. Lane and Badrinath Konety's Letter to the Editor re: Bimal Bhindi, Igor Frank, Ross J. Mason, et al. Oncologic Outcomes for Patients with Residual Cancer at Cystectomy Following Neoadjuvant Chemotherapy: A Pathologic Stage-matched Analysis. Eur Urol 2017;72:660–4
Authors: Bimal Bhindi, Stephen A. Boorjian
Journal: European Urology (2017)
Necessity of oxaliplatin in adjuvant chemotherapy for stage IIIb colorectal cancer
Authors: Hiromichi Sonoda, Tomoharu Shimizu, Toru Miyake, Katsushi Takebayashi, Sachiko Kaida, Yuki Kawai, Ayano Sonoda, Osamu Inatomi, Satoshi Murata, Masaji Tani
Journal: Annals of Oncology (2017)
The loss of EBP50 expression potentiates cell transformation
Authors: Erica L. Kreimann, Fabiana C. Morales, Yoko Takahashi, Maria-Magdalena Georgescu
Journal: Cancer Research (2005)

2592   EBP50 is an adaptor protein containing two PDZ domains that interacts with the Ezrin-radixin-moesin (ERM) family of proteins. The ERM proteins link membrane proteins to the actin cytoskeleton. They are involved in epithelial cell polarization, cell shape determination, and are important components of transduction pathways triggered by EGF and PDGF. It has been shown that PDGF stimulation induces ruffling of the cell membrane and that these actin-rich protrusions or ruffles are the major driving force for cell movements. Because EBP50 also binds to PDGF receptor and enhances its effect, we believe that EPB50 could be involved in ruffle formation and cell migration. We generated EBP50 deficient mice, in order to define the importance of the interaction between EBP50 and ERM proteins in cell growth and motility, as well as the effect on cell transformation. Mouse embryonic fibroblasts (MEFs) from the EBP50 (−/−) and EBP50 (+/+) littermates were isolated from E14 embryos. After individual isolation, the MEFs with identical genotype were pooled and the resulting EBP50 (−/−) and (+/+) populations were immortalized with SV40 t-antigens. We performed migration and proliferation assays to characterized the EBP50 (−/−) and (+/+) MEFs in the parental, and SV40 t-antigen immortalized populations. We also studied the anchorage-independent growth of the immortalized by culturing these cells in soft agar for 5 weeks. The cell migration was studied using the wound-healing assay. No difference in proliferation between EBP50 (−/−) and (+/+) was apparent. However, we found alterations in the migration pattern of the parental and immortalized EBP50 (−/−) and (+/+) cells. Briefly, the migration of the EBP50 (−/−) MEFs is more spread and there is more cell movements compared with the (+/+); in the immortalized ones the migration of the EBP50 (−/−) MEFs is faster compared to the (+/+). In addition, only the EBP50 (−/−) MEFs were capable of forming colonies in soft agar, while no colonies grew in the EBP50 (+/+) plates. These findings clearly show that the lack of the EBP50 function potentiates cell transformation. Also that the EBP50 gene could act as a tumor suppressor gene in the cell. The molecular mechanisms underlying these effects are under investigation.
The Hepatocarcinogenicity of a Series of 4′-Alkyl-4-Dimethylaminoazobenzenes&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Ellis V. Brown, Ali A. Hamdam
Journal: JNCI Journal of the National Cancer Institute (1961)

The fallowing 4′-alkylated derivatives of dimethylaminoazobenzene (DAB) have been tested for hepatocarcinogenic activity in the rat: 4′-Me(1), 4-Et(16), 4′-n-Pr(6), 4′-iso-Pr(9), 4′-n-Bu(1), 4′-iso-Bu(0), 4′-sec-Bu(0), 4′-tert-Bu(1), and 4′-phenylDAB(0). Parentheses after each indicate its rough quantitative activity. No explanation is apparent for this difference in activity.
Physical activity calendar
Authors: Bruno Paula Caraça Smirmaul
Journal: British Journal of Sports Medicine (2017)

The famous proposal by Theodosius Dobzhansky that ‘Nothing in biology makes sense except in the light of evolution’ implies that ‘no meaningful picture as a whole’ is achievable if biology is seen out of this context.1 This is not to say that scientific advances are not possible without an evolutionary perspective, but rather that its consideration may illuminate previously ‘invisible’ interpretations. Due to evolutionary insights, significant progress has been made in several areas, particularly in the field of health and disease, and its respective applications in medicine and public health.

Similarly, by using an evolutionary perspective, researchers in the field of physical activity and related areas have put forward alternative and interesting avenues for research, with potential practical applications. For instance, some examples are: (1) physical activity behaviour, promotion and adherence2; (2) mode, duration, intensity and frequency of physical activity to optimise general health3; (3) the relationship between physical activity and neurobiology4; (4) new hypothesis for athletic training5; and (5) …
Pain and fatigue in sport: are they so different?
Authors: Kieran O’Sullivan, Peter B O’Sullivan, Tim J Gabbett
Journal: British Journal of Sports Medicine (2017)

Pain and fatigue are common reasons for athletes to avoid, or reduce, sporting participation. Despite commonly coexisting, they are usually treated as distinct entities. Both sensations are often interpreted by medical staff as indicating that physical activity should be reduced or avoided, either due to tissue damage (pain) or excessive training (fatigue). But paradoxically, that management plan—relative rest—means that athletes avoid what keeps them healthy, fit and resilient—physical activity.

Coaches sometimes view the sensations of pain and fatigue as indicators of physical and/or psychological weakness; they should be ignored to ‘toughen up’ athletes, sometimes leading to athletes unhelpfully provoking symptoms. These opposing views between medical staff and coaches—which often reflect limited understanding regarding the interaction of training load, beliefs and other external factors on pain and fatigue—often place the athlete in a conflicted state. ‘Should I tell (the medical team) or should I remain stoic’ (figure 1). We discuss the parallels between pain and fatigue, and how their management reflects the lens through which these …
Comment on Craig et al. Prevalence of Celiac Disease in 52,721 Youth With Type 1 Diabetes: International Comparison Across Three Continents. Diabetes Care 2017;40:1034–1040
Authors: Giulio Maltoni, Roberto Franceschi, Giuseppe D’Annunzio, Sonia Toni, Ivana Rabbone, Stefano Zucchini
Journal: Diabetes Care (2017)

We read with interest the data by Craig et al. (1) about the prevalence of celiac disease (CD) in 52,721 youth with type 1 diabetes (T1D). The authors found a prevalence of 3.5% based on four national registries (range 1.9–7.7). We would like to share the experience of five centers of pediatric diabetes care of northern Italy (Bologna, Florence, Genoa, Trento, and Turin): we recently collected data on 2,164 children and adolescents with T1D and found 213 subjects affected by both CD and T1D (punctual prevalence 9.8% [range 6.8–12.8]). As in Italy there is no registry for pediatric diabetes, and in order to avoid a “hot spot effect” (big centers attract …
Stagnation des taux de vaccination contre la grippe dans les groupes à haut risque en Pologne et en Suède en 2003/4 et 2004/5
Authors: M Kroneman, G A van Essen
Journal: Eurosurveillance (2007)

Le present document traite des taux de vaccination contre la grippe en Pologne et en Suede pendant les saisons grippales 2003/4 et 2004/5. Un echantillon moyen constitue de 2,500 personnes a ete interroge dans chaque pays, pour chaque saison.