tbuckley/cabot-search huggingface dataset:
AB0119 Primary sjogren’s syndrome associated with anterior horn cell disorder
Authors: JC Tseng, HH Cheng, RJ Hu, LY Lu
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Central nervous system (CNS) involvement in primary Sjogren's syndrome (pSS) is controversial with regard to incidence, aetiology and pathogenesis. In the literature, the incidence of CNS-SS varies widely, ranging from rare to incidence rates of 20% to 25%. The clinical picture is diverse, ranging from mild cognitive symptoms to fatal cerebrovascular accidents. <h3>Objectives</h3> We describe a patient with pSS presenting with dysphagia and progressive respiratory failure resulting from anterior horn cell disorder. To the best of our knowledge this is the first case reported in medical literature. The disease responded to corticosteroids and hydroxychloroquine treatment. <h3>Methods</h3> A 58-year-old woman had a one year history of dry eyes and dry mouth. She experienced progressive dysphagia and dyspnea ten days prior to admission. She developed progressive respiratory muscle weakness which resulted in respiratory failure and received mechanical ventilation during admission. Examination revealed symmetrically decreased muscle power without sensory impairment and positive Schirmer test. Blood investigations revealed positive ANA, anti-SS-A and elevated IgG level up to 2820 mg/dl. Full blood cell count and creatine kinase level were normal. Sjogren's syndrome was confirmed by minor salivary gland biopsy. Electromyography, nerve conduction velocity and evoked potential studies showed anterior horn cell disorder. MRI of brain revealed negative finding. The disease improved with administration of corticosteroids and hydroxychloroquine. <h3>Results</h3> <h3>Conclusion</h3> Sjoren's syndrome should be considered in the differential diagnosis of patients with motor neuron diseases. Promop diagnosis and treatment are required to prevent further morbidity and mortality. <h3>References</h3> Cox PD, Hales RE. CNS Sjogren's syndrome: an underrecognized and underappreciated neuropsychiatric disorder. J Neuropsychiatry Clin Neurosci. 1999;11(2):241–7 Wright RA, O'Duffy JD, Rodriguez M. Improvement of myelopathy in Sjogren's syndrome with chlorambucil and prednisolone therapy. Neurology 1999;52(2):386–8 Ioannidis JP, Moutsopoulos HM. Sjogren's syndrome: too many associations, too limited evidence. The enigmatic example of CNS involvement. Semin Arthritis Rheum. 1999;29(1):1–3 Niemela RK, Hakala M. Primary Sjogren's syndrome with severe central nervous system disease. Semin Arthritis Rheum. 1999;29(1):4-13
Abstract A02: pRb-loss causes widespread changes to the transcriptome and proteome of cells
Authors: Wayne O. Miles
Journal: Cancer Research (2017)

Abstract Loss of the Retinoblastoma 1, pRb, tumor-suppressor gene is widespread in tumor cells and causes de-regulation of the E2F transcription factors. Aberrant E2F activity results in the over expression of genes required for proliferation. To determine how pRb-loss changes cells, we depleted pRb from RPE cells using shRNAs and measured the effect on the transcriptome and proteome using RNA-sequencing and quantitative Mass Spectrometry. These approaches produced a number of unexpected findings including; (A) many E2F target genes are transcribed but poorly translated, (B) pRb-loss induces a strong interferon response, and (C) pRb-deficiency increases the protein levels of the extracellular matrix components. In addition, our results support previous reports linking pRb to mitochondrial activity and metabolic reprogramming. The changes to the transcriptome and proteome are extensive and complex and we are currently conducting an in-depth analysis of these results however our preliminary analysis suggests that loss of the pRb tumor-suppressor gene causes widespread and previously unappreciated changes in the transcriptome and proteome of cells. To begin to understand the mechanisms regulating these changes in translation potential, we have begun assessing the post-transcriptional mechanisms controlling the levels of the E2F-target genes. This group of genes is induced upon pRb-loss however no associated increase in protein levels is detected. To identify the mechanisms controlling the translation potential of this collection of genes, we search for enriched motifs of post-transcriptional regulators in these mRNAs. This analysis found a strong enrichment for the Pumilio (PUM) RNA-binding protein. RNA-immunoprecipitation experiments confirm that the levels of E2F target genes bound by PUM increase upon pRb-loss. To assay how PUM levels regulate the protein levels of the E2F target genes, we depleted PUM1 or PUM2 using siRNAs and conducted quantitative Mass Spectrometry. From this analysis, we find a strong increase in the levels of some E2F target genes upon PUM and pRb-loss. Collectively, these results are providing new insights into the proteomic changes induced after pRb-loss and is highlighting some of the post-transcriptional mechanisms buffering these effects. Citation Format: Wayne O. Miles. pRb-loss causes widespread changes to the transcriptome and proteome of cells. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr A02.
Re-treatment of patients with decompensated chronic hepatitis C virus cirrhosis using 24 weeks of sofosbuvir and NS5A inhibitor, with or without ribavirin after failing a 12 week course
Authors: M.C. Cheung, A. Filipe, A. Walker, D.J. Mutimer, K. Agarwal, M. Aldersley, D. MacDonald, S. Khakoo, J. McLauchlan, G.R. Foster, W.L. Irving
Journal: Journal of Hepatology (2017)
Ribosomal Deficiency Due to Activation of the Thrombopoietin Axis May be Involved in the Reduced Levels of GATA1 Expressed By Megakaryocytes (MKs) from the Gata1low Model of Myelofibrosis
Authors: Anna Rita F Migliaccio, Maria Zingariello, Laura Sancillo, Fabrizio Martelli, Fiorella Ciaffoni, Francesca Masiello, Ilaria Ceglia, Lilian Varricchio, Rosa Alba Rana, Changsheng Zhao, John Crispino
Journal: Blood (2016)
Early Changes of the Cortical Micro‐Channel System in the Bare Area of the Joints of Patients With Rheumatoid Arthritis
Authors: David Werner, David Simon, Matthias Englbrecht, Fabian Stemmler, Christoph Simon, Andreas Berlin, Judith Haschka, Nina Renner, Thomas Buder, Klaus Engelke, Axel J. Hueber, Jürgen Rech, Georg Schett, Arnd Kleyer
Journal: Arthritis & Rheumatology (2017)

Objective To characterize the specific structural properties of the erosion‐prone bare area of the human joint, and to search for early microstructural changes in this region during rheumatoid arthritis (RA). Methods In the initial part of the study, human cadaveric hand joints were examined for exact localization of the bare area of the metacarpal heads, followed by detection of cortical micro‐channels (CoMiCs) in this region by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) and, after anatomic dissection, validation of the presence of CoMiCs by micro–computed tomography (micro‐CT). In the second part of the study, the number and distribution of CoMiCs were analyzed in 107 RA patients compared to 105 healthy individuals of similar age and sex distribution. Results Investigation by HR‐pQCT combined with adaptive thresholding allowed the detection of CoMiCs in the bare area of human cadaveric joints. The existence of CoMiCs in the bare area was additionally validated by micro‐CT. In healthy individuals, the number of CoMiCs increased with age. RA patients showed significantly more CoMiCs compared to healthy individuals (mean ± SD 112.9 ± 54.7/joint versus 75.2 ± 41.9/joint; P &lt; 0.001), with 20–49‐year‐old RA patients exhibiting similar numbers of CoMiCs as observed in healthy individuals older than age 65 years. Importantly, CoMiCs were already found in RA patients very early in their disease course, with enrichment in the erosion‐prone radial side of the joint. Conclusion CoMiCs represent a new form of structural change in the joints of patients with RA. Although the number of CoMiCs increases with age, RA patients develop CoMiCs much earlier in life, and such changes can even occur at the onset of the disease. CoMiCs therefore represent an interesting new opportunity to assess structural changes in RA.
ADHD drugs are associated with lower car crash risk
Authors: Jacqui Wise
Journal: BMJ (2017)

People with attention deficit hyperactivity disorder (ADHD) had a lower risk of motor vehicle crashes when they had received their medication, research published in JAMA Psychiatry shows.1

The researchers identified 2 319 450 US patients with ADHD by looking at commercial health insurance claims over a decade and noted any visits to emergency departments as a result of a motor vehicle crash. The patients’ mean age was 32.5 years, and 51.7% were female.

Among the patients with ADHD, 83.9% (more than 1.9 million) received at least one prescription for ADHD medicine during the follow-up …
Laparoscopic ablation for hepatocellular carcinoma: proposal of a 6-months mortality score for patient selection based on more than 1000 procedures
Authors: A. Bertacco, A. Marchini, A. Vitale, F. D’Amico, E. Gringeri, D. Neri, D. Bassi, G. Zanus, C. Aliberti, U. Cillo
Journal: Journal of Hepatology (2017)
Serum hepatitis B virus RNA level is associated with hepatitis B virus genotype and BCP mutations in untreated patients with HBeAg positive chronic hepatitis B
Authors: M.J. van Campenhout, F. van Bömmel, M. Grossmann, J. Fischer, D. Deichsel, A. Boonstra, A.J. van Vuuren, T. Berg, B.E. Hansen, H.L. Janssen
Journal: Journal of Hepatology (2017)
Erratum: Development of spontaneous autoimmune peripheral polyneuropathy in B7-2-deficient NOD mice (The Journal of Experimental Medicine (September 3, 2001) 194:5 (677-684))
Authors: B. Salomon, L. Rhee, H. Bour-Jordan, H. Hsin, A. Montag, B. Soliven, J. Arcella, A. M. Girvin, J. Padilla, S. D. Miller, J. A. Bluestone
Journal: The Journal of Experimental Medicine (2001)
Proteomic profiling of plasma proteins associated with spontaneous hepatitis B surface antigen seroclearance in chronic hepatitis B
Authors: F. Liu, W.-K. Seto, D.K.-H. Wong, R. Sharma, F.-Y. Huang, K.-S. Cheung, J. Fung, C.-L. Lai, M.-F. Yuen
Journal: Journal of Hepatology (2017)
MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION OF WHITE MICE
Authors: Leslie T. Webster
Journal: The Journal of Experimental Medicine (1925)

1. Survivors of an experimental mouse typhoid infection, selected and bred for a number of consecutive generations, give birth to offspring which are more resistant to the disease than a random group of the same inbred race. 2. Offspring of females most susceptible to this infection give birth to individuals which are more susceptible than a group of similar unselected mice.
Analysis of tumor growth rate for radioiodine (RAI)-refractory differentiated thyroid cancer patients receiving placebo and/or sorafenib in the phase III DECISION study.
Authors: Christian Kappeler, Dennis P. Healy, Christoph Baumer, Gerold Meinhardt, Rossella Elisei, Martin Schlumberger, Marcia S. Brose
Journal: Journal of Clinical Oncology (2015)

6015 Background: In the phase III DECISION trial, patients were randomized to receive double-blind (DB) sorafenib (SOR) or placebo (PLC) until tumor progression, at which time PLC patients were allowed to switch to open-label (OL) SOR and SOR patients to continue OL. We conducted an exploratory analysis of target lesion size over time to gain insight into tumor growth rate during treatment. Methods: Target lesions were assessed by central radiologic review every 8 weeks based on RECIST criteria. Changes in target lesions over time were approximated by a parabola-like 3-parametric model and tumor growth rates (TGR) derived for DB and OL treatment periods. TGR was defined as % change per month of sum of target lesion diameters. Results: Patients receiving SOR DB and then OL totaled 207 and 55, and patients receiving PLC DB and then SOR OL totaled 210 and 150, respectively; patients evaluable for TGR were 176, 38, 189 and 123, respectively. For SOR patients, TGR was typically negative early reflecting target lesion shrinkage from baseline [-3.9 (-4.7, -3.1), mean % change/mo (95% CI)] and then positive from nadir to progression [2.6 (1.9, 3.3)] reflecting tumor growth, as was TGR for the subgroup of SOR patients continuing OL treatment from 2nd baseline [1.7 (-0.9, 4.3)]. For PLC patients, TGR was typically positive [5.0 (2.2, 7.8)], as was TGR for the subgroup prior to switching to SOR at progression [6.1 (1.9, 10.3)]. The TGR pattern of PLC patients on OL SOR was similar to the DB SOR pattern, i.e. negative post second baseline [-4.4 (-5.6, -3.2)] and positive from nadir to progression [1.8 (0.5, 3.1)]. Conclusions: SOR reversed tumor growth (negative TGR) during the DB period and for PLC patients switching to SOR. TGR from nadir to progression for patients receiving SOR or post-progression for patients continuing on SOR was less than for patients on PLC, suggesting that despite evidence of tumor growth or prior RECIST progression, SOR continued to slow tumor growth relative to growth in its absence. The clinical relevance of these findings for treatment decisions needs to be further investigated. TGR may be an additional efficacy parameter to consider when monitoring SOR treatment. Clinical trial information: NCT 00895674.
Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial
Authors: Kristin K Jørgensen, Inge C Olsen, Guro L Goll, Merete Lorentzen, Nils Bolstad, Espen A Haavardsholm, Knut E A Lundin, Cato Mørk, Jørgen Jahnsen, Tore K Kvien, Ingrid P Berset, Bjørg TS Fevang, Jon Florholmen, Synøve Kalstad, Nils J Mørk, Kristin Ryggen, Kåre S Tveit, Sigrun K Sæther, Bjørn Gulbrandsen, Jon Hagfors, Kenneth Waksvik, David Warren, Karoline J. Henanger, Øivind Asak, Somyeh Baigh, Ingrid M Blomgren, Trude J Bruun, Katrine Dvergsnes, Svein O Frigstad, Clara G Gjesdal, Berit H J Grandaunet, Inger M Hansen, Ingvild S H Hatten, Gert Huppertz-Hauss, Magne Henriksen, Sunniva S Hoie, Jan Krogh, Julia R Kruse, Maud-Kristine A Ljoså, Irina P Midtgard, Pawel Mielnik, Bjørn Moum, Geir Noraberg, Armin Poyan, Ulf Prestegård, Haroon U Rashid, Jan Henrik Rydning, Liv Sagatun, Kathrine A Seeberg, Kristine Skjetne, Eldri K Strand, Hilde Stray, Njaal Stray, Roald Torp, Cecilia Vold, Carl M Ystrøm, Camilla C Zettel
Journal: The Lancet (2017)
Impact of new agents (NAs) on post-docetaxel (DOC) survival of octogenarians with metastatic castration resistant prostate cancer (mCRPC) patients (pts): Results of an Italian multicenter retrospective study (DELPHI study).
Authors: Antonello Veccia, Orazio Caffo, Salvatore Luca Burgio, Giuseppe di Lorenzo, Cinzia Ortega, Florinda Scognamiglio, Rodolfo Mattioli, Giovanni Mansueto, Fable Zustovich, Michele Aieta, Gaetano Facchini, Giuseppe Procopio, Alessandro D'Angelo, Gilbert Spizzo, Ugo De Giorgi, Sabino De Placido, Fiorella Ruatta, Enzo Galligioni
Journal: Journal of Clinical Oncology (2015)

e16017 Background: After DOC became the reference first line treatment for mCRPC pts, cabazitaxel (CABA), abiraterone acetate (AA), and enzalutamide (ENZ) significantly prolonged overall survival (OS) after DOC. Since a quote of pts develops mCRPC at very old age, often after 80 years, it could be questionable if the administration of these expensive NAs is justifiable in this population. We retrospectively evaluated the impact of post-DOC treatments on OS of octogenarians mCRPC pts treated with first-line DOC in 30 Italian hospitals. Methods: In this multicentric retrospective study, after Ethical Committee approval, we have reviewed the clinical records of all octogenarians mCRPC pts from participating institutions, treated with DOC in clinical practice, recording the pre and post-DOC clinical history, the DOC treatment details and outcomes. Results: We collected a consecutive series of 121 octogenarians pts treated between May 2003 and November 2013. The median age was 82 yrs (range 80-90). All pts had received 3-week or weekly DOC (44% and 56%, respectively) with a PSA reduction > 50% and an objective response achieved in 55% and 15% of the pts, respectively. The median PFS and OS were 7 mos and 20 mos, respectively. After DOC, 57 pts (47%) did not receive further systemic treatment, 21 (17%) received at least one old therapy (DOC rechallenge, mitoxantrone or other chemotherapies), and 43 (36%) received at least one NA (36 AA, 7 CABA, 9 ENZ). We compared these groups in terms of OS and post-DOC progression OS 3-month landmark analysis to avoid the bias due to early deaths after progression (see table). Conclusions: Although our population is highly selected and our data was obtained from a retrospective analysis, our results suggests that NAs are able to significantly prolong OS also in octogenarians mCRPC pts. This is valuable in the light of the debate concerning the appropriate use of NAs in the daily clinical practice. Post-DOC treatment Median OS Median post-DOC progression OS* No further therapy (57 pts) 14 9 Old therapies (21 pts) 20 14 NAs (43 pts) 33 26 P value < 0.0001 < 0.0001 *3-month landmark analysis
Oncologist impressions of automatic palliative care consultation for inpatients with advanced cancer.
Authors: Meghan Rose Zander, Gabrielle Betty Rocque, Toby Christopher Campbell, Renae M Quale, James F. Cleary
Journal: Journal of Clinical Oncology (2014)

e20541 Background: Access to palliative care is growing nationally, yet optimal methods for integration remain unclear. Input from oncologists is critical to the acceptance and utility of any delivery model. The University of Wisconsin implemented automatic palliative care consultation (APCC) for hospitalized patients with advanced, incurable cancer. To evaluate this process change, physician satisfaction and approaches to palliative care were evaluated before and after implementation of APCC. Methods: Attending oncologists were surveyed after supervising on the inpatient oncology service (Survey 1). For each patient discharged, oncologists were questioned about their satisfaction with hospitalization and discharge, perception of the patient’s expectations for long-term care, and impact of APCC. The patient’s primary oncologists were also surveyed post-hospitalization. (Survey 2). Results: For survey 1, 39 surveys were completed by 11 inpatient oncologists on patient who received an automatic palliative care consult. In 67% of cases, the oncologist felt that patient care was enhanced. APCC led to a specific change in management in 21% of cases. For Survey 2, 19 attending oncologists completed the survey; four were excluded due to lack of patients receiving APCC. When asked about APCC in metastatic disease, 74% felt positively about the intervention while 26% were neutral, and none experienced negative feelings. 60% reported improved understanding of patient’s long-term goals, 66% reported clarification of patient’s advanced care plan, and 27% reported it resulted in more frequent discussions regarding hospice. Conclusions: The nature of APCC is distinct from consults is for symptom burden or a transition to hospice discussion. Automatic consults require heightened sensitivity to the specifics of the case to avoid adding tension. The introduction of APCC was frequently associated with a change in management, including increased discussions regarding hospice, as well as increased knowledge of patient’s long-term goals. The large majority of academic oncologists viewed the implementation favorably suggesting that automatic consultation is feasible in inpatient oncology.
Prognostic value of HER2 expression in patients with bladder cancer treated with radical cystectomy: A biomarker study.
Authors: Philipp Erben, Ralph M Wirtz, Thomas Martini, Marcus J Trunk, Ralf Hofheinz, Maurice Stephan Michel, Christian Bolenz
Journal: Journal of Clinical Oncology (2014)

e15515 Background: Conflicting results regarding the (over-)expression of receptors of the HER-family in carcinoma of the urinary bladder (UCB) have been reported. In view off limited treatment options in UCB, HER1 and HER2 represent interesting targets for further studies. Herein, we evaluated the expression of HER family members (Erbb1-4) in association with established histopathological characteristics in patients with UCB treated with radical cystectomy (RC). Methods: HER family members RNA expression levels where determined after extraction from formalin-fixed, paraffin-embedded tissue as previously described (Koutras BJC 2008). Univariate and multivariate Cox proportional hazard models were used to assess recurrence-free survival (RFS) and cancer-specific survival (CSS). Results: A total of 94 patients (female = 22; male =72; median age: 66.5 years [range 39-88]) with UCB (pT1-4; Nx) treated with RC where included. Median Follow up was 28.2 months (range 0.9–139).UCB recurrence and cancer-specific death were recorded in 54 (57%) and 31 patients (33%), respectively. Higher pathological tumor stage (p=0.013), a positive lymph node status (p=0.0001), the presence of LVI (p=0.011) and high HER2 levels (p=0.010), were significantly associated with inferior RFS in univariate analysis. Contrarily, a negative lymph node status (p=0.0003) and low HER2 (p=0.042) levels had a favourable prognostic impact on CSS. In multivariate analysis, pN stage (p=0.024) was an independent predictor of RFS and for reduced CSS (p=0.0028). Conclusions: The results suggest that HER2 might be a negative prognostic factor in patients with UCB although significance was missed in multivariate analysis. This finding warrants further analyses in larger data sets and might be a step towards using HER2 targeted drugs in patients with UCB. Univariate analysis RFS CSS Hazard ratio p value Hazard ratio p value Gender 1.3 0.37 0.82 0.69 Age (<75) 1.2 0.68 2.1 0.085 pT Stage 2.1 0.013 1.9 0.082 Grade 1.2 0.75 1.3 0.45 pN 3.6 0.0001 3.9 0.0003 LVI 2.2 0.011 1.7 0.17 PSM 1.5 0.32 1.04 0.96 HER1 1.9 0.054 1.6 0.27 HER2 2.09 0.010 2.12 0.042 HER3 1.13 0.67 0.97 0.93 HER4 1.49 0.20 1.5 0.15 Abbreivation: PSM, positive surgical margin.
Development and validation of a simple score to select HBV-infected patients for antiviral therapy in Africa
Authors: Y. Shimakawa, R. Njie, M. Vray, P. Bonnard, J. Nana, V. Leroy, J. Bottero, P. Ingiliz, G. Post, A. Jeng, G. Ndow, I. Chemin, M. Mendy, M. Thursz, M. Lemoine
Journal: Journal of Hepatology (2017)