tbuckley/cabot-search huggingface dataset:
Abstract 5213: Overexpression of SIP1 and down-regulation of E-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy
Authors: Koji Skakamoto, Yorihisa Imanishi, Masayuki Shimoda, Kaori Kameyama, Toshiki Tomita, Hiroyuki Ozawa, Seiichi Shinden, Masato Fujii, Katsushi Shibata, Nobuya Sakai, Kaoru Ogawa
Journal: Cancer Research (2011)

Abstract Neck lymph node involvement is considered as the most important adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). Patients with clinical stage I/II (T1-2N0M0) oral tongue carcinoma usually undergo partial glossectomy alone. However, 14 to 48% of these patients develop delayed neck metastasis (DNM) within 2 years and tend to result in unfavorable course. Clinicopathologic features and molecular biomarkers have been investigated to find the reliable predictor of DNM, however, it still remains to be elucidated. Recently E-cadherin and its transcriptional repressors are thought to play a crucial role in tumor progression and metastasis, the mechanism of which is called epithelial to mesenchymal transition (EMT). The present study was aimed to examine whether the molecular factors involved in the induction of EMT, as well as standard clinicopathologic factors, are predictive of DNM in stage I/II oral tongue squamous cell carcinoma. mRNA expressions of E-cadherin and its repressors (snail, SIP1 and twist) in 7 HNSCC cell lines were evaluated by quantitative real-time RT-PCR, which revealed significant inverse correlation between E-cadherin and SIP1 (p = 0.023). Immunohistochemical staining was performed to evaluate protein expressions of E-cadherin and its repressors in the specimens of the primary lesions of 37 stage I/II tongue carcinoma patients who had initially undergone only partial glossectomy in the Keio University Hospital without elective neck dissection. Univariate analysis showed that loss of E-cadherin (p = 0.004) and overexpression of SIP1 (p &amp;lt; 0.001) were significantly correlated with DNM, although no inverse correlation was found between E-cadherin and each of its repressors. Regarding other clinicopathologic factors, mode of invasion 3/4 (p = 0.048), vascular invasion (p = 0.021) and muscular invasion (p = 0,012) were also significantly correlated with DNM. Multiple logistic regression analysis including clinicopathologic and the molecular factors elucidated that overexpression of SIP1 (p = 0.005), loss of E-cadherin (p = 0.046) and vascular invasion (p = 0.024) were independently correlated with DNM. These results suggest that DNM in the stage I/II oral tongue carcinoma is closely relating to EMT, and especially SIP1 and E-cadherin are considered as the useful markers to predict development of DNM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5213. doi:10.1158/1538-7445.AM2011-5213
Abstract 15094: Wingless (Wnt) Signaling Pathway Molecules Dickkopf-Related Protein 1 Correlates Inversely With Proximal Aortic Diameter and Left Ventricular Remodeling in Patients With Bicuspid Aortic Valve
Authors: Saeeda Fatima, Deborah Hyanik, Jennifer Victory, Paul Klotaman, Randolph Hutter, Daniel Katz
Journal: Circulation (2018)

Introduction: Dickkopf-related protein 1 (DKK1) is a member of the Wingless (Wnt) signaling pathway molecules. Wnt molecules have been shown to play a significant role in vascular smooth muscle cel...
Antibodies in pemphigus vulgaris
Authors: M. Ivars, A. España, P. Alzuguren, B. Pelacho, J.J. Lasarte, M.J. López‐Zabalza
Journal: British Journal of Dermatology (2020)

Pemphigus vulgaris is a blistering skin disorder, which can be severe. Antibodies are a type of protein used by the immune system when fighting off disease or infection, but they can sometimes turn against healthy cells. People with pemphigus vulgaris develop antibodies to various proteins that cement certain skin cells (epidermal cells) together, these include desmoglein 1, desmoglein 3 and desmocollin, together with other unidentified proteins. The damage caused by these antibodies causes separation of epidermal cells, visible under the microscope (and known as acantholysis), eventually resulting in blister formation. The antibodies may act directly on these proteins or indirectly by activation of other inflammatory substances including a disintegrin and metalloproteinase 10 (ADAM10). The authors, based in Pamplona, northern Spain, aimed to see if blistering induced by different antibodies in patients with pemphigus vulgaris involved activation of ADAM10. They found that antibodies to desmocollin triggered early splitting of the skin, independent of ADAM10. The timing and severity of splitting of skin cells induced by desmoglein antibodies 1 and 3, however, was dependent on the level of antibodies and also on activation of ADAM10. In these, inhibition of ADAM10 prevented acantholysis. The authors propose a role for development of ADAM10 inhibitors in the treatment of the subgroup of patients with pemphigus vulgaris who have antibodies to desmogleins 1 and 3. This is a summary of the study: The involvement of ADAM10 in acantholysis in mucocutaneous pemphigus vulgaris depends on the autoantibody profile of each patient.
Zoledronic Acid Prevents Bone Loss in Premenopausal Women with Early Breast Cancer Undergoing Adjuvant Chemotherapy: A Phase III Study of Korean Cancer Study Group (KCSG-BR06-01).
Authors: J. Ahn, K. Jung, S. Kim, K. Lee, J. Ro, Y. Park, J. Ahn, Y. Im, S. Im, M. Lee, S. Kim
Journal: Cancer Research (2009)

Abstract Background: Adjuvant chemotherapy results in early menopause in the majority of premenopausal patients due to premature ovarian failure and consequent skeletal morbidity. Zoledronic acid (ZA) is known to prevent bone loss in postmenopausal women. The purpose of this study was to determine whether ZA can prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.Methods: This study is a randomized, open-label, phase III multicenter trial. Premenopausal women older than age 40 were randomly assigned to ZA group (two infusions of 4 mg IV, every 6 months) or observation group after surgery. All patients were treated with the same adjuvant chemotherapy regimen (AC--&amp;gt;T; 4 cycles of AC followed by 4 cycles of paclitaxel or docetaxel). The first infusion of ZA was given on day 1 of the first chemotherapy. All patients received supplementations with oral calcium 600 mg/d and vitamin D 400 IU/d. The bone mineral density (BMD) was measured at the baseline, 6th and 12th months. Bone turnover markers were measured before chemotherapy and in 3, 6, 12 months.Results: Between March 2007 and May 2008, a total of 110 premenopausal women were enrolled in this study and the majority of women (91.8%) developed amenorrhea at 1 year post chemotherapy. The mean percent change of BMD in lumbar spine was +0.5% in the ZA group versus -3.6% in the observation group at 6 months (p&amp;lt;0.01) and, -1.0% versus -7.5%, at 12 months (p&amp;lt;0.01). Differences in percent change of BMD from baseline between two groups were 6.5% (95% CI, 5.2 to 7.9%) for the lumbar spine, and 3.6% (95% CI, 2.2% to 5.1%) for the femoral neck (p&amp;lt;0.01). Type I collagen metabolite PINP levels at 12 months were significantly higher in the observation group than in the ZA group; 72.7 mg/l (range 21.8∼250 mg/l) versus 30.8 mg/l (range 14.7∼62.7 mg/l) (p=0.0001). Changes of other bone turnover markers including urinary N-telopeptide, bone alkaline phosphatase, and serum C-telopeptide were also significantly different between two groups (p&amp;lt;0.01). ZA was generally well tolerated, and adverse event profile was similar between two groups.Conclusion: Adjuvant chemotherapy with AC--&amp;gt;T induced amenorrhea in the majority of patients over 40 years in this study. Treatment with two infusions of ZA 4 mg every 6 months effectively prevented bone loss within the first year of adjuvant chemotherapy for early breast cancer in premenopausal women. Regular BMD measurements and early bisphosphonate therapy should be considered for this population. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2104.
Reducing the negative appendectomy rate with the laparoscopic appendicitis score; a multicenter prospective cohort and validation study
Authors: Koen Gelpke, Jenneke T.H. Hamminga, James J. van Bastelaar, Bart de Vos, Maarten E. Bodegom, Erik Heineman, H. Sijbrand Hofker, Mostafa El Moumni, Jan Willem Haveman
Journal: International Journal of Surgery (2020)
L-Thyroxine Therapy for Older Adults With Subclinical Hypothyroidism and Hypothyroid Symptoms
Authors: Maria de Montmollin, Martin Feller, Shanthi Beglinger, Alex McConnachie, Drahomir Aujesky, Tinh-Hai Collet, Ian Ford, Jacobijn Gussekloo, Patricia M. Kearney, Vera J.C. McCarthy, Simon Mooijaart, Rosalinde K.E. Poortvliet, Terence Quinn, David J. Stott, Torquil Watt, Rudi Westendorp, Nicolas Rodondi, Douglas C. Bauer
Journal: Annals of Internal Medicine (2020)

Background: L-thyroxine does not improve hypothyroid symptoms among adults with subclinical hypothyroidism (SCH). However, those with greater symptom burden before treatment may still benefit. Objective: To determine whether L-thyroxine improves hypothyroid symptoms and tiredness among older adults with SCH and greater symptom burden. Design: Secondary analysis of the randomized, placebo-controlled trial TRUST (Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism Trial). (ClinicalTrials.gov: NCT01660126) Setting: Switzerland, Ireland, the Netherlands, and Scotland. Participants: 638 persons aged 65 years or older with persistent SCH (thyroid-stimulating hormone level of 4.60 to 19.9 mIU/L for >3 months and normal free thyroxine level) and complete outcome data. Intervention: L-thyroxine or matching placebo with mock dose titration. Measurements: 1-year change in Hypothyroid Symptoms and Tiredness scores (range, 0 to 100; higher scores indicate more symptoms) on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire among participants with high symptom burden (baseline Hypothyroid Symptoms score >30 or Tiredness score >40) versus lower symptom burden. Results: 132 participants had Hypothyroid Symptoms scores greater than 30, and 133 had Tiredness scores greater than 40. Among the group with high symptom burden, the Hypothyroid Symptoms score improved similarly between those receiving L-thyroxine (mean within-group change, −12.3 [95% CI, −16.6 to −8.0]) and those receiving placebo (mean within-group change, −10.4 [CI, −15.3 to −5.4]) at 1 year; the adjusted between-group difference was −2.0 (CI, −5.5 to 1.5; P = 0.27). Improvements in Tiredness scores were also similar between those receiving L-thyroxine (mean within-group change, −8.9 [CI, −14.5 to −3.3]) and those receiving placebo (mean within-group change, −10.9 [CI, −16.0 to −5.8]); the adjusted between-group difference was 0.0 (CI, −4.1 to 4.0; P = 0.99). There was no evidence that baseline Hypothyroid Symptoms score or Tiredness score modified the effects of L-thyroxine versus placebo (P for interaction = 0.20 and 0.82, respectively). Limitation: Post hoc analysis, small sample size, and examination of only patients with 1-year outcome data. Conclusion: In older adults with SCH and high symptom burden at baseline, L-thyroxine did not improve hypothyroid symptoms or tiredness compared with placebo. Primary Funding Source: European Union FP7.
PD-1 Blockade in Anaplastic Thyroid Carcinoma
Authors: Jaume Capdevila, Lori J. Wirth, Thomas Ernst, Santiago Ponce Aix, Chia-Chi Lin, Rodryg Ramlau, Marcus O. Butler, Jean-Pierre Delord, Hans Gelderblom, Paolo A. Ascierto, Angelica Fasolo, Dagmar Führer, Marie Luise Hütter-Krönke, Patrick M. Forde, Anna Wrona, Armando Santoro, Peter M. Sadow, Sebastian Szpakowski, Hongqian Wu, Geraldine Bostel, Jason Faris, Scott Cameron, Andreea Varga, Matthew Taylor
Journal: Journal of Clinical Oncology (2020)

Anaplastic thyroid carcinoma is an aggressive malignancy that is almost always fatal and lacks effective systemic treatment options for patients with
Do adults have ADHD? A history lesson.
Authors: Matthew P C Smith
Journal: BMJ (2010)

Debates on the legitimacy of a diagnosis of attention deficit hyperactivity disorder (ADHD) in children or adults are still raging1 2 because of a lack of understanding of the history of the disorder. Drug companies have indeed marketed the concept of adult ADHD to potential consumers1—as they did childhood ADHD to parent-teacher associations in the United States during the 1960s and 1970s—but this is only part of the story.
Use of Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis: A Systematic Review and Meta‐Analysis
Authors: Erin Wolf, Nicole E. Rich, Jorge A. Marrero, Neehar D. Parikh, Amit G. Singal
Journal: Hepatology (2020)

Hepatocellular carcinoma (HCC) surveillance is associated with early tumor detection and improved survival; however, it is often underused in clinical practice. We aimed to characterize surveillance use among patients with cirrhosis and the efficacy of interventions to increase surveillance.We performed a systematic literature review using the MEDLINE database from January 2010 through August 2018 to identify cohort studies evaluating HCC surveillance receipt or interventions to increase surveillance in patients with cirrhosis. A pooled estimate for surveillance receipt with 95% confidence intervals was calculated. Correlates of surveillance use were defined from each study and prespecified subgroup analyses. Twenty-nine studies, with a total of 118,799 patients, met inclusion criteria, with a pooled estimate for surveillance use of 24.0% (95% confidence interval, 18.4-30.1). In subgroup analyses, the highest surveillance receipt was reported in studies with patients enrolled from subspecialty gastroenterology/hepatology clinics and lowest in studies characterizing surveillance in population-based cohorts (73.7% versus 8.8%, P < 0.001). Commonly reported correlates of surveillance included higher receipt among patients followed by subspecialists and lower receipt among those with alcohol-associated or nonalcoholic steatohepatitis (NASH)-related cirrhosis. All eight studies (n = 5,229) evaluating interventions including patient/provider education, inreach (e.g., reminder and recall systems), and population health outreach strategies reported significant increases (range 9.4%-63.6%) in surveillance receipt.HCC surveillance remains underused in clinical practice, particularly among patients with alcohol-associated or NASH-related cirrhosis and those not followed in subspecialty gastroenterology clinics. Interventions such as provider education, inreach including reminder systems, and population health outreach efforts can significantly increase HCC surveillance.
35th Bethesda Conference: cardiology's workforce crisis: a pragmatic approach**This document was approved by the American College of Cardiology Foundation Board of Trustees, March 2004. When citing this document, the American College of Cardiology would appreciate the following citation format: Fye WB, Hirshfeld JW, et al. Cardiology's workforce crisis: a pragmatic approach. Presented at the 35th Bethesda Conference, Bethesda, Maryland, October 17–18, 2003. J Am Coll Cardiol 2004;44:215–75. …
Authors: W.Bruce Fye, John W. Hirshfeld Jr
Journal: Journal of the American College of Cardiology (2004)
A Unique Case of Secondary Pulmonary Alveolar Proteinosis after E-Cigarette, or Vaping, Product Use–associated Lung Injury
Authors: Anna-Karoline Israel, Moises J. Velez, Serban A. Staicu, Robert Ambrosini, Matthew McGraw, Tanupriya Agrawal
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Abstract 455: A Comparison of CPR Quality Using an Augmented Reality Application versus a Standard Audio-Visual Feedback Manikin
Authors: Shaun K McGovern, Steve Balian, Abhishek Bhardwaj, Benjamin Abella, Audrey L Blewer, Marion Leary
Journal: Circulation (2019)

Background: The provision of high-quality cardiopulmonary resuscitation (CPR) is a significant predictor of survival from cardiac arrest, yet healthcare provider (HCP) CPR quality is known to be poor. Although refresher CPR simulation training has been shown to improve HCP CPR quality, no studies have compared an immersive augmented reality (AR) application to a standard audio-visual feedback (AVF) manikin (Laerdal ResusciAnne) as a refresher training modality. Objectives: We randomized HCPs to refresher CPR simulation training with either a novel AR CPR training application (CPReality, Figure 1) or a validated AVF manikin; both cohorts completed a post-simulation CPR quality evaluation with no feedback immediately following the intervention. We sought to assess the efficacy of AR as a CPR simulation modality compared with an AVF manikin. We hypothesized that the AR application would confer similar skills to the AVF manikin. Results: We enrolled 100 experienced HCPs (e.g. RN, MD, APP) between 1/19-5/19. Mean chest compression (CC) rate for the AR application compared with the AVF manikin was 114±1 vs 121±3 cpm (p&lt;0.01) and CC depth was 52±1 vs 48±1 mm (p&lt;0.01), respectively. Post-simulation mean CC rate for the AR application compared with the AVF manikin was 122±15 vs 117±11 cpm (p=ns), depth was 52±8 vs 49±8 mm (p=ns), and percent with complete recoil was 92±24 vs 88±28 (p=ns), respectively. More AR simulation subjects agreed that the AR simulation provided a realistic patient presence compared to AVF simulation subjects (79% vs. 59%, p=0.07). The majority of CPReality simulation participants agreed or strongly agreed that they would want to use AR modalities for future CPR training (95%). Conclusions: In a post-test scenario, the AR CPR simulation training produced similar CPR quality as the standard AVF manikin in refreshing CPR skills in HCP. Further studies should explore the use of innovative technologies for CPR training. Figure 1 . CPReality (CPReality).
De Novo Gene Variants and Familial Bipolar Disorder
Authors: Claudio Toma, Alex D. Shaw, Bronwyn J. Overs, Philip B. Mitchell, Peter R. Schofield, Antony A. Cooper, Janice M. Fullerton
Journal: JAMA Network Open (2020)

This case-control study explores de novo candidate gene variants in 18 multiplex families with bipolar disorder.
Dissecting RoomToxinology down underStruan K Sutherland, James Tibballs, Australian Animal Toxins: the Creatures, their Toxins, and Care of the Poisoned Patient, Second Edition, Oxford University Press Australia & New Zealand, Sydney (2001), Pp 880. AUS$375·00, ISBN: 019550643X
Authors: Richard Dart
Journal: The Lancet (2002)
Effects of periodontal disease on glycemic control, complications, and incidence of diabetes mellitus
Authors: Robert J. Genco, Filippo Graziani, Hatice Hasturk
Journal: Periodontology 2000 (2020)

Abstract Diabetes mellitus is a group of metabolic disorders with high mortality and morbidity associated with complications such as cardiovascular disease, kidney disease, and stroke. The prevalence of diabetes is 9.4% in US adults, and prevalence increases markedly with age, with 1 in 4 adults aged ≥65 years affected by diabetes. The estimated number of adults with type 2 diabetes globally almost tripled between 2002 and 2017, reflecting increases seen in the USA and elsewhere. This increase raises concerns about the increased morbidity and mortality associated with the complications of diabetes, including periodontal disease and tooth loss. There is a reciprocal adverse relationship between diabetes and periodontal disease, with diabetes as a major risk factor for periodontal disease, and in those patients with diabetes who also have periodontal disease then there are adverse effects on glycemic control and complications such as cardiovascular disease and end stage renal disease. In this review, those studies detailing the adverse effects of periodontal disease and diabetes will be discussed. Also, evidence is accumulating that periodontitis may play a role in increasing the incidence of new cases of type 2 diabetes, and possibly gestational diabetes. Of course, these studies need to be expanded to better understand the effects of periodontitis on diabetes glycemic control, complications, prediabetes, and the incidence of new cases. However, given the tremendous burden of diabetes on society, the dental profession should be proactive in preventing and treating periodontal disease, not only to preserve the dentition, but also to minimize the adverse effects of periodontitis on diabetes and its complications.
Aplidin induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac and Rho activation, and MKP-1 phosphatase down-regulation
Authors: Laura Gonzalez-Santiago, Yajaira Suarez, Natasha Zarich, Ana Cuadrado, Teresa Martinez, Jose Maria Rojas, Carmen Cuevas, Alberto Munoz
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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Aplidin (APL) is a novel marine antitumor drug currently ongoing Phase II clinical trials in a variety of cancers. APL has been granted orphan drug status for the treatment of Acute Lymphoblastic Leukaemia and Multiple Myeloma in US and the European Union. APL is an extremely powerful antitumoral agent that rapidly triggers an apoptotic process at nanomolar concentrations. We have previously identified Jun N-terminal kinase (JNK), among other kinases activated by APL (EGFR, Src, p38MAPK), as a primary and crucial mediator of its apoptosis-inducing activity in human MDA-MB-231 breast cancer cells (J Biol. Chem., 278, 241-250, 2003; Oncogene 23, 4673-4680, 2004). Our data show that exogenous glutathione (GSH) and also agents that increase cellular GSH levels, but not other antioxidants inhibit APL cytotoxicity. We found that Aplidin alters glutathione homeostasis in human breast cancer cells increasing the ratio between the oxidized and reduced forms (GSSG/GSH). Aplidin changes glutathione peroxidase and reductase activity and induces GSH extrusion into the medium. We also found that Aplidin generates radical oxygen species (ROS) and disrupts the mitochondrial membrane potential, and that exogenous GSH inhibits these effects and also JNK activation and cell death. In addition, Aplidin transiently decreases the cellular Ca2+ content and causes oxidation of membrane phospholipids and DNA, as estimated by the increase in the cellular content of malondialdehyde and 8-oxo-2Â′-deoxyguanosine. To examine the mechanism of JNK activation by Aplidin we analysed its effects on several JNK regulators. Aplidin did not affect the interaction of JNK with glutathione-S-tranferase (GST)-λ1/λ2, reported to cause JNK inhibition. In addition, exogenous expression of wild-type or dominant negative versions of apoptosis stimulating kinase (ASK)-1 did not affect the activation of JNK by Aplidin. In contrast, we found a rapid activation by Aplidin of Rac and Rho small GTPases, two known upstream mediators of JNK. This effect was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, a compound that inhibits GSH synthesis. Moreover, Aplidin decreases the cellular level of MKP-1, a major phosphatase inactivating JNK, with a kinetics compatible with the sustained activation of JNK observed in drug-treated cells. We conclude that Aplidin induces apoptosis via increase of GSSG/GSH ratio, a necessary step for induction of oxidative stress and sustained JNK activation, This is consequence of at least two mechanisms: Rac and Rho activation and MKP-1 down-regulation.