tbuckley/cabot-search huggingface dataset:
Incidence trends of keratinocytic skin cancers and melanoma in Israel 2006-2011.
Authors: Tal Sella, Iris Goren, Varda Shalev, Hagit Shapira, Judith Zandbank, Joseph Rosenblum, Michael Kimlin, Gabriel Chodick
Journal: Journal of Clinical Oncology (2014)

1598 Background: The incidence of skin cancer, both melanoma and keratinocyte cancers (KC) is rising throughout the world, specifically squamous cell carcinomas(SCC) and basal cell carcinoma(BCC), being the most common of all cancers. Objective: To determine trends in incidence of Melanoma, BCC and SCC among 1.7 million members of Maccabi Healthcare Services from 2006 to 2011. Methods: Data on newly diagnosed Melanoma, SCC and BCC cases was collected from the MHS Cancer Registry and based on histology reports from the centralized pathology lab. Age-specific and overall age-adjusted European standardized rates were computed. Trends were estimated by calculating Average Annual Percentage Change(AAPC). Results: During the six year study period, a total of 16,079 subjects were diagnosed with at least one BCC, 4,767 with SCC and 1,264 with invasive melanoma. Age-standardized incidence rates were 188, 58 and 17 per 100,000 person years for BCC, SCC and melanoma, respectively. All lesions were more common among males and primarily affected the elderly. BCC rates were stable throughout the study period(AAPC -0.7%, 95%CI -4.5% to 3.2%) while SCC incidence increased significantly(AAPC 15.5%, 95%CI: 2.6% to 30.0%). In contrast, melanoma rates showed a continuously decreased with a significant AAPC of -3.0%, 95%CI (-4.5 to -0.1). Conclusions: Previously unreported, the incidence of KC in Israel is one of the highest in the world. The disparities in incidence trends between SCC, BCC and melanoma allude to their different etiologies. These findings underscore the importance of continuous monitoring, education and prevention programs in a growing high risk population.
Hodgkin lymphoma: A review and update on recent progress
Authors: Satish Shanbhag, Richard F. Ambinder
Journal: CA A Cancer Journal for Clinicians (2017)

Abstract Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed‐Sternberg cells in an inflammatory background. Patients are commonly diagnosed with HL in their 20s and 30s, and they present with supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in advanced‐stage disease, HL is highly curable with combination chemotherapy, radiation, or combined‐modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk‐adapted approaches have helped de‐escalate therapy in low‐risk patients while intensifying treatment for higher risk patients. Even patients who are not cured with initial therapy can often be salvaged with alternate chemotherapy combinations, the novel antibody‐drug conjugate brentuximab, or high‐dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death‐1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL. Alternate donor sources and reduced‐intensity conditioning have made allogeneic hematopoietic stem cell transplantation a viable option for more patients. Future research will look to integrate novel strategies into earlier lines of therapy to improve the HL cure rate and minimize long‐term treatment toxicities. CA Cancer J Clin 2018;68:116‐132 . © 2017 American Cancer Society .
PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A features in rodent models
Authors: Hien Tran Zhao, Sagar Damle, Karli Ikeda-Lee, Steven Kuntz, Jian Li, Apoorva Mohan, Aneeza Kim, Gene Hung, Mark A. Scheideler, Steven S. Scherer, John Svaren, Eric E. Swayze, Holly B. Kordasiewicz
Journal: Journal of Clinical Investigation (2017)

Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of peripheral myelin protein 22 (PMP22) and is the most common hereditary peripheral neuropathy. CMT1A is characterized by demyelination and axonal loss, which underlie slowed motor nerve conduction velocity (MNCV) and reduced compound muscle action potentials (CMAP) in patients. There is currently no known treatment for this disease. Here, we show that antisense oligonucleotides (ASOs) effectively suppress PMP22 mRNA in affected nerves in 2 murine CMT1A models. Notably, initiation of ASO treatment after disease onset restored myelination, MNCV, and CMAP almost to levels seen in WT animals. In addition to disease-associated gene expression networks that were restored with ASO treatment, we also identified potential disease biomarkers through transcriptomic profiling. Furthermore, we demonstrated that reduction of PMP22 mRNA in skin biopsies from ASO-treated rats is a suitable biomarker for evaluating target engagement in response to ASO therapy. These results support the use of ASOs as a potential treatment for CMT1A and elucidate potential disease and target engagement biomarkers for use in future clinical trials.
Identification of functional histamine H4 receptor in the 1321N1 human astrocytoma cell line
Authors: Ron Cole, Ruin Moaddel, Harrison Musyimi, Chester Frazier, Julia Hartenstein, Mukesh Gandhari, Michel Bernier, Irving Wainer
Journal: Cancer Research (2008)

4806   The treatment of the 1321N1 astrocytoma cell line with histamine results in a reduction of cAMP accumulation (1). This effect has been attributed to the presence and function of the H1-histamine receptor subtype (H1R) (1). An alternative possibility is the presence of functional H4R in the cell line as activation of this receptor also results in decreased cAMP accumulation. However, the H4R has not been identified in the CNS (2). This study reports the initial observation of functional H4R in the 1321N1 astrocytoma cell line.  The presence of the H1R and H4R in the 1321N1 cell line was investigated by Western blot analysis using anti-human H1R and H4R antibodies. Confocal microscopy and flow cytometry studies were conducted using fluorescent-labeled histamine as the marker and the H1R-specific ligand mepyramine and the H4R-specific ligands 4-methylhistamine and JNJ 10191584. The effect of the H4R-specific agonist 4-methylhistamine on cAMP accumulation was also investigated with an ELISA assay.  The results of the study demonstrate that both H1R and H4R are expressed in the 1321N1 cell line and that the treatment of this cell line with 4-methylhistamine for 5 minutes resulted in a significant reduction in forskolin-mediated cAMP accumulation. The data indicates that the previously observed effects of histamine on cAMP accumulation may also be mediated by the H4R.  The data shows that H4R is present in a CNS-related cell line and that the receptor may play a role in astrocytoma cell biology. The presence of this receptor in the 1321N1 cell line may represent a new specific target in the treatment of astrocytomas.  1 N. Nakahata, et al., Molec. Pharmacol. 29:188-195, 1986  2 C.A. Akdis, F.E.R. Simons, Eur. J. Pharmacol. 533:69-76, 2006
Flow-Mediated Dilation of Brachial Artery as a Screening Tool for Anthracycline-Induced Cardiotoxicity
Authors: Maria Anastasiou, Evangelos Oikonomou, Flora Zagouri, Gerasimos Siasos, Alexios S. Antonopoulos, Theodora Psaltopoulou, Aristotelis Bamias, Meletios A. Dimopoulos, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2017)
Abstract 12529: The Association of the Different Vitamin D Metabolites to Death, Myocardial Infarction, Heart Failure, and Stroke: Results From the Intermountain Heart Collaborative Study
Authors: Heidi T May, Oxana Galenko, John F Carlquist, Lindell K Weaver, Stacey Knight, Tyler Barker, Kirk U Knowlton, Joseph B Muhlestein
Journal: Circulation (2016)

Introduction: Many epidemiological studies have shown that total circulating levels of 25-hydroxyvitamin D (VitD) are strongly associated with poor cardiovascular (CV) outcomes. However, 85-90% of circulating VitD is bound to vitamin D binding protein (BP) or albumin, and levels obtained may not be truly reflective of the VitD available to act on target cells. Whether more direct markers of VitD activity such as bioavailable VitD (BIO) or free VitD (FREE) are more effective in predicting future CV risk is not known. Hypothesis: The more direct markers of VitD activity are more strongly associated with adverse CV outcomes. Methods: Patients (N=4285) undergoing angiography for CAD determination were studied. Levels of VitD, BP and albumin were directly measured and BIO and FREE were calculated using standard formulae. Multivariable Cox hazard regression was utilized to determine quartile (Q) associations with death (all-cause, CAD, and cardiac), MI, HF hospitalization, and stroke. Median length of follow-up was 10.9 years. Results: Patients averaged 64±12 years, 66% male, 23% diabetic, 90% Caucasian, and 70% diagnosed with CAD. Median and interquartile ranges of VitD, BP, BIO, and FREE were 24.9 (20.0, 28.7) ng/mL, 168.3 (103.7, 245.9) ug/mL, 7.1 (3.9, 15.2) ng/mL, and 15.7 (9.2, 33.3) pg/mL, respectively. Multivariable hazard ratios for the various metabolites with each of the outcomes are shown in Table. BP was not associated with any of the outcomes. VitD, BIO, and FREE were all associated with death (all-cause, CAD, and cardiac). VitD continued to be significantly associated with HF hospitalization and stroke, with its association to MI being attenuated. Conclusion: Among this predominately Caucasian population, VitD was found to consistently be the strongest predictor of all of the outcomes over BP, BIO, and FREE. Future studies are needed to evaluate whether obtaining thresholds of VitD levels are associated with a reduction in CV risk.
NHS advises GPs not to prescribe “low value” drugs
Authors: Gareth Iacobucci
Journal: BMJ (2017)

NHS England will issue guidance to GPs and commissioners to limit the prescribing of “low value” treatments on the NHS, as part of a drive to reduce costs and unwarranted variation.

The NHS will also consult further with patients on plans to restrict access to drugs that can be bought over the counter, such as paracetamol for minor, short term conditions, which it estimates will save £190m (€215m; $255m) a year.

The proposals were approved by NHS England’s board on Thursday 30 November,1 after an initial public consultation. GPs and clinical commissioning groups will now be advised to restrict the prescribing of 18 “ineffective, unsafe, and low clinical value” treatments (see box), which NHS …
La surveillance de la listériose humaine en France, 2001-2003
Authors: V Goulet, C Jacquet, P Martin, V Vaillant, E Laurent, H de Valk
Journal: Eurosurveillance (2006)

La declaration obligatoire de la listeriose a commence en France en 1999. Le renforcement de la surveillance de la sante publique, comprenant la caracterisation moleculaire en routine des souches de L. monocytogenes, le suivi epidemiologique des cas et le recueil d’echantillons de nourriture, a ameliore la sensibilite de la detection des epidemies et la reponse a donner. L’incidence de la listeriose a diminue de 4,5 cas/million en 1999-2000 a environ 3,5 cas/million au cours de la periode 2001-2003. Les caracteristiques cliniques, demographiques et microbiologiques de la listeriose en France n’ont pas evolue sur cette periode. Les infections materno-neonatales ont represente 24% de la totalite des cas. Le serotype 4b etait present dans 49% des cas et 60% des cas groupes. L’incidence de la listeriose en France a decline et est a l’heure actuelle moins elevee que dans plusieurs pays europeens.
A comparison of percutaneous and endoscopic-guided celiac plexus block/neurolysis in pancreatic cancer patients.
Authors: Swetha Kambhampati, Elizabeth A. Sugar, Joseph M. Herman, Michael A. Erdek, Eun Ji Shin, Daniel A. Laheru
Journal: Journal of Clinical Oncology (2017)

e15767 Background: Celiac plexus block (CPB) and celiac plexus neurolysis (CPN) are options for pain control in pancreatic cancer. Conventionally they are performed percutaneously (PC) with fluoroscopic or CT guidance. However endoscopic ultrasound (EUS) guidance is being increasingly used. The aim of this retrospective study is to compare PC-guided and EUS-guided CPB/CPN for pain control. Methods: Our retrospective cohort study included pancreatic cancer patients who underwent CPN/CPB for pain control from 2008 to 2015 at Johns Hopkins. Patients were assessed immediately post-procedure and at 1 month. Patients were selected using CPT and ICD diagnosis code guided searches of the EHR. Pain intensity was assessed using a Numeric Rating Scale (NRS). A response was defined as a decrease in NRS scores by = &gt; 3 points. The validated FACT-Hep score was used to assess quality of life (QOL). Opiate usage was converted into morphine dosage equivalents. Wilcox rank-sum and Fisher’s exact test were used to compare the EUS and PC cohorts. Results: Of 107 patients, 46 (43%) had EUS-CPN, 57 (53%) PC-CPN, and 4 (4%) PC-CPB. 10 patients had procedural complications (7% EUS and 11% PC, p = 0.51) with the most common being chronic diarrhea. The baseline median NRS score was 7 with significantly higher scores for those receiving EUS compared to PC (9 vs 7, p &lt; 0.001). Immediately post-procedure, more PC patients (87%) had a response when compared to EUS patients (72%), although it did not reach statistical significance (p = 0.08). By one month, there was no difference in response rates. (43% CPN vs 34% EUS, p = 0.42) FACT-Hep score declined significantly in all patients with a median drop of 8 points at 1 month and no difference between PC and EUS (9 vs 8, p = 0.46). There was no difference in opiate usage at 1 month (88% PC vs 93% EUS, p = 0.51). Conclusions: Both EUS and PC-guided CPN were effective at reducing post-procedural pain in pancreatic cancer patients but their effectiveness waned by 1 month. EUS did have slightly fewer complications although PC did have slightly higher rates of response post-procedurally. QoL declined and opiate usage was unchanged in both groups. Both procedures had temporary efficacy and need further evaluation.
Reply
Authors: Theodorus B.M. Hakvoort, Wouter H. Lamers
Journal: Hepatology (2017)

View this article online at wileyonlinelibrary.com. Potential conflict of interest: Nothing to report. We thank Qvartskhava c.s. for drawing our attention to the different mouse lines used in their and our study and their potential effects on the resulting phenotypes. We opted for the Alfp‐Cre line with the three Afp enhancers1 to assure complete excision in all pericentral hepatocytes. Qvartskhava c.s. cite Pruneau et al.,2 who reported that Alfp‐Cre mice ectopically express human growth hormone in their pituitary and hypothalamus and suffer, as a result, from peripheral growth‐hormone deficiency, growth retardation, and a fatty liver. In their reply to Pruneau et al., Mueller and Moriggl argue that they did not observe growth retardation in their Stat5fl/+/Nr3c1fl/+/AlfpCre+/− mice and that hepatic steatosis is also observed in Stat5fl/fl/AlbCre+/− mice.3 Similarly, we did not observe growth retardation in Glul5fl/fl/AlfpCre+/− (our Fig. 1). Given that growth retardation only occurs if growth hormone, its receptor, or Stat5b are homozygously deficient (Teglund et al.4 and references therein), Pruneau c.s.2 probably studied AlfpCre+/+ rather than the AlfpCre+/− mice that are usually used for gene excision. Furthermore, we did not observe the pericentral macrovesicular fat deposition in Stat5–/– mice5 that we observed in Glul5fl/fl/AlfpCre+/− mice. Another important difference between the study of Qvartskhava c.s. and our study is that they used C57BL/6J mice, whereas we used FVB/N mice. Although circulating ammonia concentrations attributed to hepatic GS deficiency increased ∼1.7‐fold in both studies, absolute concentrations were ∼5‐fold higher in C57BL/6J than in FVB/N mice because of a deletion in the Nnt gene of C57BL/6J mice. It will be interesting to establish to what extent these substantial strain‐specific differences in background ammonia concentrations affect the adverse effects of hyperammonemia.
Neoantigens in MDS Are Associated with Two Novel CD4+ T Cell Subsets and Improved Overall Survival
Authors: Thomas Coats, Alexander E Smith, Athanasios Mourikis, Tala Shahin, Austin G. Kulasekararaj, Steve Best, Sneha Chitre, Richard Ellis, Nedyalko Petrov, Susanne Heck, Jonathan Michael Irish, Shahram Kordasti, Ghulam Mufti
Journal: Blood (2017)
Methylphenidate during pregnancy linked to small risk of cardiac malformations
Authors: Jacqui Wise
Journal: BMJ (2017)

Women who take methylphenidate during early pregnancy have a small increased risk of delivering an infant with cardiac malformations. However, the large cohort study published in JAMA Psychiatry found no increase in cardiac malformations related to amphetamine exposure and neither drug was associated with an increased risk for malformations overall.1

Stimulants, including methylphenidate and amphetamines, are considered first line drugs for treating attention-deficit/hyperactivity disorder (ADHD). In recent years, use of these drugs in adults, including women of reproductive age, has increased substantially.

For the primary analysis, the researchers used Medicaid data to …
Abstract 12330: Comparison Between Optical Frequency Domain Imaging Guided and Intravascular Ultrasound Guided Balloon Pulmonary Angioplasty for the Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Nobutaka Ikeda, Shuji Kubota, Toru Okazaki, Hisao Hara, Yukio Hiroi
Journal: Circulation (2015)

Introduction: The balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is an emerging procedure. High-resolution imaging is useful to visualize the complex structures in the pulmonary arteries of CTEPH. The use of intravascular ultrasound (IVUS) during BPA has reduced complications. Optical frequency domain imaging (OFDI) has been suggested to be a promising alternative to IVUS for the visualization of coronary arteries. Hypothesis: We assessed the hypothesis that OFDI guided BPA is comparable or superior to IVUS guided BPA. Methods: All complications related with BPA procedures and used balloon sizes for consecutive 141 lesions were recorded. In 23 lesions, both OFDI and IVUS were performed and obtained 48 pairs of images to assess the association of the measurements. Results: Among the 141 lesions, 47 lesions were treated by OFDI guided and 94 lesions were treated by IVUS guided. OFDI provided clear high-resolution images of pulmonary arteries of CTEPH (Figure). There was no significant difference in occurrence of complications between OFDI and IVUS guided (11% vs. 16%, ns). In 23 lesions (both OFDI and IVUS were performed), vessel area (VA) and lumen area (LA) measured by OFDI were smaller than those of IVUS. However, significant high correlations were found between the two measurements(VA: r=0.78 p&lt;0.0001 and LA: r=0.75 p&lt;0.0001). Less inter- and intra-observer variabilities were found in OFDI measurements than IVUS measurements. In all 141 lesions, used balloon diameters were not different between the OFDI and IVUS guided (2.9±0.8 vs. 2.8±0.9, ns). Conclusions: The safety of OFDI guided BPA was acceptable. High correlations between OFDI and IVUS measurements were observed. The reproducibility of OFDI measurements were excellent and higher than IVUS measurements. Balloon diameters which were decided OFDI and IVUS were not different. In conclusion, OFDI has a potential to refine BPA procedures.
When dyadic interaction is the context: Mimicry behaviors on the origin of imitation
Authors: Ruth Campos, Carmen Nieto
Journal: Behavioral and Brain Sciences (2017)

Abstract Keven &amp; Akins (K&amp;A) redefine some of the neonatal imitation (NI) behaviors as developmental stereotypes. From a neuroconstructivist framework, those early gestures are also far from being considered as imitative behaviors. The cognitive substrate of imitation requires an interactive context to develop. Prior to intentional imitation, the dyad shows mimicry behaviors, which are automatic, but do not fade through development.
Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer
Authors: Franz Villarroel-Espindola, Xiaoqing Yu, Ila Datar, Nikita Mani, Miguel Sanmamed, Vamsidhar Velcheti, Konstantinos Syrigos, Maria Toki, Hongyu Zhao, Lieping Chen, Roy S. Herbst, Kurt A. Schalper
Journal: Clinical Cancer Research (2017)

Purpose: Determine the localized expression pattern and clinical significance of VISTA/PD-1H in human non-small cell lung cancer (NSCLC).Experimental Design: Using multiplex quantitative immunofluorescence (QIF), we performed localized measurements of VISTA, PD-1, and PD-L1 protein in 758 stage I-IV NSCLCs from 3 independent cohorts represented in tissue microarray format. The targets were selectively measured in cytokeratin+ tumor epithelial cells, CD3+ T cells, CD4+ T-helper cells, CD8+ cytotoxic T cells, CD20+ B lymphocytes and CD68+ tumor-associated macrophages. We determined the association between the targets, clinicopathological/molecular variables and survival. Genomic analyses of lung cancer cases from TCGA were also performed.Results: VISTA protein was detected in 99% of NSCLCs with a predominant membranous/cytoplasmic staining pattern. Expression in tumor and stromal cells was seen in 21% and 98% of cases, respectively. The levels of VISTA were positively associated with PD-L1, PD-1, CD8+ T cells and CD68+ macrophages. VISTA expression was higher in T-lymphocytes than in macrophages; and in cytotoxic T cells than in T-helper cells. Elevated VISTA was associated with absence of EGFR mutations and lower mutational burden in lung adenocarcinomas. Presence of VISTA in tumor compartment predicted longer 5-year survival.Conclusions: VISTA is frequently expressed in human NSCLC and shows association with increased tumor-infiltrating lymphocytes, PD-1 axis markers, specific genomic alterations and outcome. These results support the immunomodulatory role of VISTA in human NSCLC and suggests its potential as therapeutic target. Clin Cancer Res; 24(7); 1562-73. ©2017 AACR.