tbuckley/cabot-search huggingface dataset:
Reply
Authors: Stefano Romeo, Alessio Aghemo, Thomas Berg, Felix Stickel, Luca Valenti
Journal: Hepatology (2015)

Potential conflict of interest: Dr. Stickel advises for and received grants from Gilead. He advises for Biotest and received grants from MSD, Novartis, and Janssen. Author names in bold designate shared co‐first authorship We thank Liu and Que for their remarks on our article reporting an impact of the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant on steatosis, necroinflammation, and fibrosis in patients with chronic hepatitis C.1 We agree that the robustness of the association of the E167K variant with severe fibrosis in the validation cohort, though it was independent of age and sex, is somewhat lessened by the younger age of carriers of the genetic mutation, as well as the lack of adjustment for adiposity. As correctly noted, the uneven age distribution may have even underestimated the contribution of the E167K variant to fibrosis progression. Indeed, E167K carriers had reached F2‐F4 fibrosis at a younger age (52 ± 9 [n = 68] vs. 55 ± 12 years [n = 341]; P = 0.02). However, we would also like to point out that we had already shown an association of the E167K variant with steatosis, necroinflammation, and nearly with fibrosis stage, as well as a significant association with cirrhosis in a larger Italian discovery cohort (n = 815). This was independent of demographic, genetic, anthropometric, and viral features. Furthermore, the effect size of the E167K variant was similar to that detected in the validation cohort. By excluding individuals of the validation cohort at the extremes of age distribution (<25/>75 yrs), the E167K variant was no more associated with age (51 ± 10 [n = 94] vs. 52 ± 11 years [n = 522]; P = not significant) and sex, but, at logistic regression analysis, conferred a similar risk of fibrosis (unadjusted odds ratio [OR]: 1.66; 95% confidence interval [CI]: 0.36‐0.96; P = 0.03; adjusted OR: 1.88; 95% CI: 0.32‐0.88; P = 0.01). In addition, even if we could not correct for body mass, the E167K variant does not impact on adiposity.1 Last, the E167K variant predisposes to hepatic fat accumulation in patients with nonviral liver disease,2 and this translates into increased inflammation and risk of advanced fibrosis in nonalcoholic fatty liver.3 Therefore, we believe that the conclusion that the TM6SF2 E167K variant impacts on steatosis severity and is associated with liver damage and fibrosis was supported by the results and is mechanistically plausible. Further studies will certainly contribute to better define the impact of the TM6SF2 variant on hepatic fibrosis progression, as well as the interaction with age, adiposity‐insulin resistance, and alcohol intake.
Neutron beam therapy targets brain cancer
Authors: Z. Kmietowicz
Journal: BMJ (1998)

A UK centre is pioneering a new form of radiotherapy based on neutron beams, which could previously only be generated by nuclear reactors, for patients with brain tumours.

The technique–boron neutron capture therapy–involves the injection of a boron-carrying compound into the blood which is selectively taken up by tumour cells. A beam of low energy neutrons …
MODIFIED BMI DOES NOT PREDICT ADVERSE OUTCOMES IN PATIENTS WITH CARDIAC AMYLOID UNDERGOING HEART TRANSPLANTATION: A REPORT FROM ICCAT (INTERNATIONAL CONSORTIUM FOR CARDIAC AMYLOID TRANSPLANTATION)
Authors: Sara Tabtabai, Muthiah Vaduganathan, Johannes Steiner, James Stone, Jerry Estep, Ronald Witteles, Giuseppe Feltrin, Mark Zucker, David Baran, David Seldin, Jignesh Patel, Mazen Hanna, Andrea Cordero-Reyes, Van Selby, Marc Semigran, Mathew Maurer
Journal: Journal of the American College of Cardiology (2015)
FRI0120 Prevalence and predictors of vertebral fractures after 5 years of disease activity steered treatment in patients with early active rheumatoid arthritis
Authors: L. Dirven, M. van den Broek, J.H. van Groenendael, W.M. de Beus, P.J. Kerstens, T.W. Huizinga, C.F. Allaart, W.F. Lems
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Vertebral fractures (VFs) are more common in patients with rheumatoid arthritis (RA) compared to the general population. It is suggested that an appropriate control of disease, generally more effectively achieved with disease activity score (DAS)-steered treatment strategies, may prevent the development of vertebral fractures. <h3>Objectives</h3> To determine the prevalence of VFs after 5 years of DAS-steered treatment in patients with early active RA and to investigate the association of VFs with disease activity, functional ability and bone mineral density (BMD) over time. <h3>Methods</h3> Five-year radiographs of the lateral thoracic and lumbar spine of 275 patients in the BeSt study, a randomized trial comparing four treatment strategies, were available. Treatment adjustments were made every 3 months aiming at a DAS≤2.4. Vertebral fractures were assessed using the Genant method, with a fracture defined as loss of height reduction &gt;20% in one vertebra. BMDs of the spine and hip were measured with dual energy X-ray absorptiometry. With linear mixed models, DAS and Health Assessment Questionnaire (HAQ) scores over 5 years were compared for patients with and without VFs. With GEE the association between BMD and VFs was determined. <h3>Results</h3> At baseline patients were on average 54 years old and most were female (67%), of whom 18% were postmenopausal. Mean DAS was 4.4 and mean HAQ score was 1.3. After 5 years of DAS steered treatment, VFs were observed in 41/275 patients (15%). No difference in prevalence was found when stratified for gender, prednisone use and menopausal status. Disease activity over time was higher in patients with VFs, with a mean difference of 0.20 (95% CI:0.05-0.36). HAQ scores were higher in patients with VFs, independent of disease activity, with a mean difference of 0.12 (95% CI:0.02-0.2). Although values were slightly lower over time in patients with vertebral fractures, mean BMDs in the spine and hip over time were not independently associated with VFs (OR 0.99, 95%CI:0.78-1.25 and 0.94, 95%CI:0.65-1.36, respectively). Higher age was independently associated with VFs (OR 1.06, 95%CI:1.02-1.09). <h3>Conclusions</h3> After 5 years of DAS-steered treatment, 15% of these RA patients had VFs. Higher age was associated with the presence of VFs, but mean BMDs in the hip and spine were not. VFs are associated with more disability, independent of disease activity. Patients with VFs have a higher disease activity over time, suggesting that VFs may be prevented by optimal disease activity suppression. <h3>Disclosure of Interest</h3> None Declared
Possible Influence of the Prospective Payment System on the Assignment of Discharge Diagnoses for Coronary Heart Disease
Authors: Annlouise R. Assaf, Kate L. Lapane, Joyce L. McKenney, Richard A. Carleton
Journal: New England Journal of Medicine (1993)

The prospective payment system, under which diagnosis-related groups (DRGs) are used to reimburse hospitals for the care of Medicare patients, replaced the fee-for-service method of payment in Rhode Island in 1983 and in Massachusetts in 1985. Changes in financial incentives resulting from the use of the DRG system may have influenced the assignment of discharge diagnostic codes away from those with lower reimbursement toward codes with higher reimbursement.
BM-26 * CD15 AND E-SELECTIN MEDIATION OF ADHESION OF NON-SMALL CELL LUNG CANCER CELLS TO BRAIN ENDOTHELIUM IN LUNG-BRAIN METASTASIS
Authors: G. Pilkington, S. Jassam, Z. Maherally, J. Smith, H. Fillmore
Journal: Neuro-Oncology (2014)

BACKGROUND: Lung metastases to the brain are common secondary cancers, representing over 50% of fatal complications of systemic cancer. Metastasis of cancer cells involves multiple steps including intravasation, cancer cell-endothelial rolling and adhesion, extravasation and cerebral colonization. Here, we focused on metastatic Non-Small Cell lung cancer cells adhesion to brain endothelial cells. Specifically, we investigated the role of CD15 in lung cancer and its interaction with E-selectin and brain endothelial cells adhesion. METHODS: Five lung cancer cell lines and one brain endothelial cell line (hCMEC/D3) were used (two primary, COR-L105 and A549; one lymph node lung metastatic cell line, NCI-H1299 and two biopsied secondary lung to brain metastatic cultures). Western blot (WB), immunocytochemistry (ICC) and flow cytometric analysis were used to characterise CD15 expression. To induce E-selectin, endothelial cells were treated with TNF-a. Qualitative and quantitative tumour cell-endothelial adhesion assays and live cell image microscopy were conducted, followed by antibody blocking experiments. RESULTS: All cell lines expressed detectable CD15, as determined by WB, flow cytometry and ICC, with the lung cancer to lymph node cell line expressing the highest, followed by lung to brain cell lines. E-selectin expression was significantly increased in the brain endothelial cell line (p < 0.001) with detectable levels in lung cancer cell lines. There was a significant increase in lung cancer adhesion to brain endothelium exposed to TNFa (P < 0.001); the highest increase seen in the lung-lymph node cells followed by both the lung-brain cells and the primary lung cancer cell line (A549). This adhesion was completely blocked by co-treatment of CD15 antibodies compared to IgM isotype controls. CONCLUSIONS: CD15 may play a significant role in lung cancer cell adhesion to brain endothelium.We postulate that by interfering with CD15 homodimer and heterodimer interactions, adhesion of circulating lung cancer cells to the blood brain barrier would be prevented.
“Witch’s Milk” and 99mTc-Pertechnetate Uptake in Neonatal Breast Tissue
Authors: Sachin Jain, Punit Sharma, Anirban Mukherjee, Chandrasekhar Bal, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2013)

Milk coming from the breast of newborn is called "witch's milk", and it results from transplacental transfer of maternal hormones. We present a case of a 5-day-old female neonate with secretion of "witch's milk", prominent breast nodules, and uptake of 99mTc-perchnetate in bilateral breast nodules on Meckel scan. Familiarity with this uncommon though not unexpected finding is needed to avoid confusion while interpreting Meckel scintigraphy.
Pain and Its Treatment in Outpatients with Metastatic Cancer
Authors: Charles S. Cleeland, Rene Gonin, Alan K. Hatfield, John H. Edmonson, Ronald H. Blum, James A. Stewart, Kishan J. Pandya
Journal: New England Journal of Medicine (1994)

Pain is often inadequately treated in patients with cancer. A total of 1308 outpatients with metastatic cancer from 54 treatment locations affiliated with the Eastern Cooperative Oncology Group rated the severity of their pain during the preceding week, as well as the degree of pain-related functional impairment and the degree of relief provided by analgesic drugs. Their physicians attributed the pain to various factors, described its treatment, and estimated the impact of pain on the patients' ability to function. We assessed the adequacy of prescribed analgesic drugs using guidelines developed by the World Health Organization, studied the factors that influenced whether analgesia was adequate, and determined the effects of inadequate analgesia on the patients' perception of pain relief and functional status.
Hemagglutination in Viral Hepatitis
Authors: W. Paul Havens
Journal: New England Journal of Medicine (1958)

A NUMBER of apparently nonspecific and unrelated serologic reactions are known to occur in patients with viral hepatitis, and the descriptions of these have been reviewed elsewhere.1 Among the various studies that have been made were attempts to demonstrate agglutinins for erythrocytes, and early reports described a heterophil antibody in the serums of some patients during the acute phase of hepatitis that agglutinated sheep erythrocytes. This antibody was apparently different from that found in infectious mononucleosis and could be differentiated from it by absorption on guinea-pig kidney.2 , 3 Subsequent studies by Bang4 indicated that old stored serums of patients with hepatitis . . .
Ribosomal Protein Rpl22 Controls the Dissemination of T-cell Lymphoma
Authors: Shuyun Rao, Kathy Q. Cai, Jason E. Stadanlick, Noa Greenberg-Kushnir, Nehal Solanki-Patel, Sang-Yun Lee, Shawn P. Fahl, Joseph R. Testa, David L. Wiest
Journal: Cancer Research (2016)

Mutations in ribosomal proteins cause bone marrow failure syndromes associated with increased cancer risk, but the basis by which they do so remains unclear. We reported previously that the ribosomal protein Rpl22 is a tumor suppressor in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), and that loss of just one Rpl22 allele accelerates T-cell lymphomagenesis by activating NF-κB and inducing the stem cell factor Lin28B. Here, we show that, paradoxically, loss of both alleles of Rpl22 restricts lymphoma progression through a distinct effect on migration of malignant cells out of the thymus. Lymphoma-prone AKT2-transgenic or PTEN-deficient mice on an Rpl22(-/-) background developed significantly larger and markedly more vascularized thymic tumors than those observed in Rpl22(+/+) control mice. But, unlike Rpl22(+/+) or Rpl22(+/-) tumors, Rpl22(-/-) lymphomas did not disseminate to the periphery and were retained in the thymus. We traced the defect in the Rpl22(-/-) lymphoma migratory capacity to downregulation of the KLF2 transcription factor and its targets, including the key migratory factor sphingosine 1-phosphate receptor 1 (S1PR1). Indeed, reexpression of S1PR1 in Rpl22-deficient tumor cells restores their migratory capacity in vitro The regulation of KLF2 and S1PR1 by Rpl22 appears to be proximal as Rpl22 reexpression in Rpl22-deficient lymphoma cells restores expression of KLF2 and S1P1R, while Rpl22 knockdown in Rpl22-sufficient lymphomas attenuates their expression. Collectively, these data reveal that, while loss of one copy of Rpl22 promotes lymphomagenesis and disseminated disease, loss of both copies impairs responsiveness to migratory cues and restricts malignant cells to the thymus. Cancer Res; 76(11); 3387-96. ©2016 AACR.
Evolving the future of education: Problems in enabling broad social reforms
Authors: Peter Gray
Journal: Behavioral and Brain Sciences (2014)

Abstract The apparent success of the Sudbury Valley School, coupled with its lack of impact on the larger culture, is used here to illustrate general constraints on managed change at the large-population level. Government regulations preventing innovation, the difficulty of bucking social norms, and the inadequacy of current indices of success operate against beneficial educational change in the larger culture.
Abstract 4746: Structural studies of human glioma pathogenesis-related protein 1(GLIPR1)
Authors: Oluwatoyin A. Asojo, Raymond A. Koski, Nathalie Bonafé
Journal: Cancer Research (2012)

Abstract Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide, to direct its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory protein, antigen 5, pathogenesis related-1) domain, and a transmembrane domain. Phase I/II clinical trial involving direct injection of neoadjuvant GLIPR1 prior to radical prostatectomy are underway (IND #13033). GLIPR1 gene therapy has been shown to be anti-metastatic in an orthotopic mouse model of prostate cancer. GLIPR1 is also currently being investigated for glioblastoma targeted therapy. We present here crystal structures of a truncated soluble domain of the human GLIPR1 protein, sGLIPR1, solved by molecular replacement (MR) using a truncated polyalanine model of the CAP domain of stecrisp, a snake venom CRISP (cysteine-rich secretory protein), in PHASER. The correct MR solution could only be obtained by removing all loops in the search model. While, the native structure was refined to 1.85 Å, that of the Zn2+ complex was refined to 2.2 Å. The latter structure reveals that the putative binding cavity coordinates Zn2+ similarly to snake venom CRISPs which are involved in Zn2+-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop / turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. We also propose a model for the structure of the full-length, membrane-bound GLIPR1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4746. doi:1538-7445.AM2012-4746
Exertional heat stroke in a young military trainee: is it preventable?
Authors: Buddhika T. B. Wijerathne, Senaka D. Pilapitiya, Vadivel Vijitharan, Mohammed M. F. Farah, Yashodhara V. M. Wimalasooriya, Sisira H Siribaddana
Journal: Military Medical Research (2016)

Heat stroke is a life-threatening condition with exertional heat stroke occurring frequently among soldiers and athletes. Because of its common occurrence, many military trainees practice preventive measures prior to any activity requiring severe exertion. Although it is said to be common in practice, different presentations of heat stroke are scarcely described in literature.We describe a case of an exertional heat stroke in a 23-year-old male Sinhalese soldier who developed early changes of renal failure, liver failure and rhabdomyolysis. The patient initially presented with convulsions, delirium and loss of consciousness to an outside health care facility before being transferred to our institution.It is clear that heat stroke does occur in military trainees while preventive strategies are being practiced. It is important for those who provide healthcare to soldiers to provide proper advice on how to identify impending heat stroke prior to any exercises resulting in severe physical exertion. Further, treating physicians should educate all military trainees about preventive strategies.
Marked Fluctuations in Drug Plasma Concentrations Caused by Use of Portable Pumps for Fluorouracil Continuous Infusion
Authors: M. C. ETIENNE, G. MILANO, J. L. LAGRANGE, F. BAJARD, E. FRANCOIS, A. THYSS, M. SCHNEIDER, N. RENEE, R. FETY
Journal: JNCI Journal of the National Cancer Institute (1993)
TRATAMIENTO ENDOSCÓPICO DEL DIVERTICULO DE ZENKER (DZ): UN MÉTODO AMBULATORIO EFICAZ Y SEGURO
Authors: P Díez Redondo, H Núñez Rodríguez, I Peñas Herrero, A Vargas García, C De La Serna Higuera, P Gil Simón, M Pérez-Miranda
Journal: Endoscopy (2013)

Introducción: DZ causa disfagia y complicaciones como neumonía aspirativa y malnutrición. Su tratamiento convencional es quirúrgico o mediante endoscopio rígido. Objetivo: Presentamos una serie de DZ tratados con mucomiotomía endoscópica flexible mediante Ligasure®, dispositivo que permite un sellado vascular, autólogo y permanente, previo a la sección del septo entre divertículo y esófago, que evita el sangrado y la disección tisular. Material y Método: Estudio retrospectivo: 26 diverticulotomías (mayo 2010- abril 2013) en 24 pacientes. Resultados: 17 varones y 7 mujeres, edad media 74.8 años (54 – 92). Todos presentaban disfagia (71% para sólidos, 25% mixta, 4.2% para líquidos) y: regurgitación 42%, tos crónica 21%, neumonía aspirativa 12.5% o pérdida ponderal 12.5%. Tiempo medio de evolución: 17.7 meses (0.25 – 37). Tamaño diverticular medio: 2.3 cm. Se precisaron 1 – 3 sesiones con 1.3 cortes/sesión (entre 1 – 3). En el 70% se colocaron uno o más clips, profilácticamente salvo en dos: uno para sellar una pequeña perforación y otro para hemostasia. Tres complicaciones inmediatas: dos leves (dolor intenso cervical y sangrado autolimitado) y una severa (neumomediastino por pequeña perforación con cierre exitoso con clips) y ninguna complicación posterior. El procedimiento fue ambulatorio salvo en los pacientes con dolor cervical severo y neumomediastino, que fueron ingresados. Al mes del procedimiento 23/24 pacientes no presentaban disfagia. Tras seguimiento medio de 13.8 meses existieron dos recidivas: una al mes, tras ligera mejoría inicial, y otra como regurgitación a los 8 meses. En ambos se practicó nueva mucomiotomía: pobre resultado en una mujer de 92 años con presbiesófago, y buen resultado en un varón con divertículo > 3 cm. Conclusiones: La mucomiotomía endoscópica mediante Ligasure® proporciona un tratamiento seguro y eficaz del DZ. La recidiva sintomática es poco frecuente y en casos seleccionados puede resolverse con una nueva sesión. Esta técnica, habitualmente ambulatoria, podría resultar más costoefectiva que el tratamiento convencional.
A2.30 TFH-like cells in the ra synovium are selectively associated with IL-21 production and ectopic lymphoid structures
Authors: N Lepse, A Nerviani, C Pitzalis, M Bombardieri
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> A subset of rheumatoid arthritis (RA) patients are characterised by the presence of ectopic lymphoid structures (ELS) in the synovium. Synovial ELS display germinal centres with the <i><i>in situ</i></i> selection of ACPA-producing autoreactive B cells. T follicular helper (Tfh) cells play a critical role in germinal centre reactions in secondary lymphoid organs via expression of costimulatory molecules (eg, ICOS) and the release of IL-21, a potent B cell activator. Increased levels of IL-21 have been found in various autoimmune diseases and IL-21 is considered a potential therapeutic target in RA. The aim of this study was to characterise Tfh-like and IL-21-producing T cells in the RA synovium in the context of presence or absence of ELS. <h3>Materials and methods</h3> RA synovial tissue was evaluated for the presence of Tfh-like cells (defined by co-expression of PD-1 and ICOS) by immunofluorescence microscopy. Synovial fluid mononuclear cells were either directly stained for surface marker expression or stimulated for 4h with Leukocyte Activation Cocktail in the presence of brefeldin A to evaluate cytokine expression by flow cytometry. IL-21 receptor (IL-21R) expression on fibroblast-like synoviocytes (FLS) was analysed by flow cytometry. <h3>Results</h3> The numbers of PD-1+ICOS+ cells were significantly higher in ELS-positive than ELS-negative synovial tissue ([median ± SEM] 18.50 ± 9.6 vs 0.0 ± 1.4, p = 0.009). Consistent with the histological findings, increased percentages of CD4<sup>+</sup>PD-1+ICOS+ cells (63.63%±17.21 vs 9.0%±1.8) and IL-21-producing CD4<sup>+</sup> T cells were found in synovial fluid of arthritis patients when compared to peripheral blood of healthy donors ([median ± SEM] 19.53%±5.6 vs 5.43%±1.3). Furthermore, a sizeable subset of FLS (65.85%±16.92) expressed IL-21R and IL-21R mRNA expression in FLS could be significantly upregulated by TLR stimulation. <h3>Conclusions</h3> Tfh-like cells are significantly more represented in ELS-positive than in ELS-negative synovium. IL-21-producing CD4<sup>+</sup> T cells in synovial fluid might have a direct pro-inflammatory effect on FLS via IL-21/IL-21R signalling.
386 PARACRINE ACTIVATION OF HUMAN HEPATIC STELLATE CELLS BY HEPATITIS C VIRUS VIA ANGIOPOIETIN RECEPTOR, TIE-2
Authors: S. Martin-Vilchez, Y. Rodriguez-Muñoz, R. Lopez-Rodriguez, A. Bartolome-Hernandez, R. Aldabe, M.L. Garcia-Buey, R. Moreno-Otero, P. Sanz-Cameno
Journal: Journal of Hepatology (2012)