tbuckley/cabot-search huggingface dataset:
“Hepatic Superscan” in a Patient With Hepatosplenic Alphabeta T-cell Lymphoma
Authors: Entao Liu, Siyun Wang, Peilong Lai, Zhouyang Lian, Shuxia Wang
Journal: Clinical Nuclear Medicine (2018)

A 36-year-old woman with a 2-week history of fever and markedly elevated lactate dehydrogenase levels. Nonenhanced CT and contrast-enhanced CT showed hepatosplenomegaly, diffusely decreased attenuation of the liver, and homogeneous enhancement in the hepatic and splenic parenchyma. F-FDG PET/CT revealed diffuse intense heterogeneous uptake by the liver (like superscan in bone scintigraphy). A liver needle biopsy confirmed the diagnosis of hepatosplenic alphabeta T-cell lymphoma. Subsequently, she received chemotherapy. The follow-up F-FDG PET/CT showed decreased F-FDG uptake in the liver and spleen.
Role of immune-related conditions in smoldering myeloma and MGUS.
Authors: Mary Kwok, Neha Korde, Elisabet E. Manasanch, Manisha Bhutani, Irina Maric, Katherine R. Calvo, Adriana Zingone, Rene Costello, Benjamin M. Cherry, Mary Ann Yancey, Marcia Mulquin, Mark J. Roschewski, Ola Landgren
Journal: Journal of Clinical Oncology (2012)

8104 Background: Recent guidelines emphasize tailored follow-up and the need for clinical trials for high-risk smoldering myeloma (SMM). Emerging evidence from epidemiological studies suggests that immune-related conditions play a role in the causation of myeloma precursor disease (SMM and monoclonal gammopathy of undetermined significance; MGUS) and are of clinical importance for the risk of developing multiple myeloma. The aim of our study is to assess whether there is an altered biology in SMM/MGUS patients with preceding immune-related conditions. Methods: From our ongoing prospective SMM/MGUS natural history study, we evaluated 56 SMM and 60 MGUS patients. Information on autoimmunity was identified at baseline. All patients underwent extensive clinical and molecular characterization. At baseline, all patients underwent bone marrow biopsy evaluation using immunohistochemistry and multi-color flow cytometry of plasma cells. We assessed expression patterns of adverse plasma cell markers (CD56 and CD117), and applied risk models based on serum immune markers and bone marrow findings. Results: Among enrolled SMM and MGUS patients, 7 (12%) and 9 (15%) had a preceding autoimmune disorder. We found SMM patients with (vs. without) a preceding autoimmune disorder to have a substantially lower rate of CD56 (28% vs. 61%) and CD117 (28% vs. 61%) expressing plasma cells. When we compared the same markers in MGUS patients, CD56 and CD117 expression patterns were similar among patients with vs. without preceding autoimmunity (10% vs. 17%, and 50% vs. 48%). Using the Mayo Clinic risk model, none of the SMM patients with a preceding autoimmune disorder had high-risk features; in contrast, 3/41 (7%) of those without a preceding autoimmune disorder were high-risk SMM. Using the Mayo Clinic risk model, none of the MGUS patients were high-risk independent of autoimmune status. Conclusions: Our prospective clinical study found SMM patients with preceding immune-related conditions to have less adverse biology, supportive of epidemiological studies suggesting the risk of developing multiple myeloma is substantially lower in these patients.
Analysis of DNA Methylation at Specific Loci in Stool Samples Detects Colorectal Cancer and High-Grade Dysplasia in Patients With Inflammatory Bowel Disease
Authors: John B. Kisiel, Pasquale Klepp, Hatim T. Allawi, William R. Taylor, Maria Giakoumopoulos, Tamara Sander, Tracy C. Yab, Bjorn A. Moum, Graham P. Lidgard, Stephan Brackmann, Douglas W. Mahoney, Arne Roseth, David A. Ahlquist
Journal: Clinical Gastroenterology and Hepatology (2018)
Airway and peripheral uPAR is elevated in asthma, and identifies a severe, non-atopic subset of patients
Authors: Michael A. Portelli, Christopher Moseley, Ceri E. Stewart, Dirkje S. Postma, Peter Howarth, Jane A. Warner, John W. Holloway, Gerard H. Koppelman, Chris Brightling, Ian Sayers
Journal: Allergy (2016)

Rationale: Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studies have identified uPAR elevation in asthma; however, a definitive study regarding which clinical features of asthma uPAR may be driving is currently lacking.  Objectives: We aimed to comprehensively determine the uPAR expression profile in asthma and control subjects utilizing bronchial biopsies and serum, and to relate uPAR expression to asthma clinical features.  Methods: uPAR levels were determined in control (n = 9) and asthmatic (n = 27) bronchial biopsies using immunohistochemistry, with a semi-quantitative score defining intensity in multiple cell types. Soluble-cleaved (sc) uPAR levels were determined in serum through ELISA in UK (cases n = 129; controls n = 39) and Dutch (cases n = 514; controls n = 96) cohorts.  Measurements and main results: In bronchial tissue, uPAR was elevated in inflammatory cells in the lamina propria (P = 0.0019), bronchial epithelial (P = 0.0002) and airway smooth muscle cells (P = 0.0352) of patients with asthma, with uPAR levels correlated between the cell types. No correlation with disease severity or asthma clinical features was identified. scuPAR serum levels were elevated in patients with asthma (1.5-fold; P = 0.0008), and we identified an association between high uPAR serum levels and severe, nonatopic disease.  Conclusions: This study provides novel data that elevated airway and blood uPAR is a feature of asthma and that blood uPAR is particularly related to severe, nonatopic asthma. The findings warrant further investigation and may provide a therapeutic opportunity for this refractory population.
Increasing macrolide resistance among Streptococcus agalactiae causing invasive disease in non-pregnant adults was driven by a single capsular-transformed lineage, Portugal, 2009 to 2015
Authors: Elísia Lopes, Tânia Fernandes, Miguel P Machado, João André Carriço, José Melo-Cristino, Mário Ramirez, Elisabete R Martins
Journal: Eurosurveillance (2018)

We characterised Lancefield group B streptococcal (GBS) isolates causing invasive disease among non-pregnant adults in Portugal between 2009 and 2015. All isolates (n = 555) were serotyped, assigned to clonal complexes (CCs) by multilocus sequence typing and characterised by surface protein and pilus island gene profiling. Antimicrobial susceptibility was tested by disk diffusion and resistance genotypes identified by PCR. Overall, serotype Ia was most frequent in the population (31%), followed by serotypes Ib (24%) and V (18%). Serotype Ib increased significantly throughout the study period (p &lt; 0.001) to become the most frequent serotype after 2013. More than 40% of isolates clustered in the CC1/ alp 3/PI-1+PI-2a genetic lineage, including most isolates of serotypes Ib (n = 110) and V (n = 65). Erythromycin and clindamycin resistance rates were 35% and 34%, respectively, both increasing from 2009 to 2015 (p &lt; 0.010) and associated with CC1 and serotype Ib (p &lt; 0.001). The Ib/CC1 lineage probably resulted from acquisition of the type Ib capsular operon in a single recombination event by a representative of the V/CC1 macrolide-resistant lineage. Expansion of the new serotype Ib/CC1 lineage resulted in increased macrolide resistance in GBS, causing invasive disease among adults in Portugal. The presence of this clone elsewhere may predict more widespread increase in resistance.
Radiation Followed by OX40 Stimulation Drives Local and Abscopal Antitumor Effects in an Anti–PD1-Resistant Lung Tumor Model
Authors: Sharareh Niknam, Hampartsoum B. Barsoumian, Jonathan E. Schoenhals, Heather L. Jackson, Niranjan Yanamandra, Mauricio S. Caetano, Ailin Li, Ahmed I. Younes, Alexandra Cadena, Taylor R. Cushman, Joe Y. Chang, Quynh N. Nguyen, Daniel R. Gomez, Adi Diab, John V. Heymach, Patrick Hwu, Maria Angelica Cortez, James W. Welsh
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system has increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti–PD1-resistant lung tumors. Experimental Design: We established a bilateral tumor model in 129Sv/Ev mice using an anti–PD1-resistant lung tumor cell line. Primary tumors were treated with intratumoral injection of an OX40 agonist antibody, given as adjuvant therapy after XRT (36 Gy in three 12-Gy fractions), whereas secondary tumors were left untreated to investigate abscopal outcomes. Results: The combination of XRT followed by OX40 stimulation effectively inhibited local and systemic antitumor growth, limited lung metastases, and improved survival rates. This treatment regimen augmented CD4+ and CD8+ T-cell expansion. XRT induced the expression of OX40 on T cells in tumors and spleens and increased the percentages of splenic CD103+ dendritic cells. Conclusions: Our data extend the benefits of radiation to systemic disease control, especially when combined with anti-OX40 agonist to promote immunologically mediated abscopal effects. Moreover, this study provides a rational treatment approach and sequence to overcome anti–PD1-resistant poorly immunogenic tumors. Clin Cancer Res; 24(22); 5735–43. ©2018 AACR.
Does Lindioil (indirubin) treatment affect the composition of <i>Malassezia</i> species on psoriatic skin?
Authors: Y.K. Lin, B.H. Lee
Journal: British Journal of Dermatology (2018)

Linked Articles:Gaitanis et al. Br J Dermatol 2018; 179:800. Lin et al. Br J Dermatol 2018; 178:124–31.
Atraumatic (pencil-point) versus conventional needles for lumbar puncture: a clinical practice guideline
Authors: Bram Rochwerg, Saleh A Almenawer, Reed A C Siemieniuk, Per Olav Vandvik, Thomas Agoritsas, Lyubov Lytvyn, Waleed Alhazzani, Patrick Archambault, Frederick D’Aragon, Pauline Darbellay Farhoumand, Gordon Guyatt, Jon Henrik Laake, Claudia Beltrán-Arroyave, Victoria McCredie, Amy Price, Christian Chabot, Tracy Zervakis, Jetan Badhiwala, Maude St-Onge, Wojciech Szczeklik, Morten Hylander Møller, Francois Lamontagne
Journal: BMJ (2018)

### What you need to know Is the needle tip configuration important when performing a lumbar puncture for any indication? A systematic review published in the Lancet in December 2017 suggests that it is. The review found that using atraumatic (pencil-point) lumbar puncture needles instead of conventional lumbar puncture needles reduced the risk of post-dural-puncture headache and of return to hospital for additional pain control.1 This guideline recommendation aims to promptly and transparently translate this evidence to a clinical recommendation, following standards for GRADE methodology and trustworthy guidelines.2 The BMJ Rapid Recommendations panel makes a strong recommendation for the use of atraumatic needles for lumbar puncture in all patients regardless of age (adults and children) or indication instead of conventional needles.34 Box 1 shows the article and evidence linked to this Rapid Recommendation. The main infographic provides an overview of the absolute benefits and harms (although none were present here) of atraumatic needles. Table 1 below shows any evidence that has emerged since the publication of this guideline. Box 1 ### Linked resources for this BMJ Rapid Recommendations clusterRETURN TO TEXT
Transient Asymptomatic Pulmonary Opacities During Osimertinib Treatment and its Clinical Implication
Authors: Hansang Lee, Ho Yun Lee, Jong-Mu Sun, Se-Hoon Lee, Youjin Kim, Song Ee Park, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Journal: Journal of Thoracic Oncology (2018)
Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial
Authors: Atsushi Nakajima, Mitsunori Seki, Shinya Taniguchi, Akira Ohta, Per-Göran Gillberg, Jan P Mattsson, Michael Camilleri
Journal: The Lancet. Gastroenterology & hepatology (2018)
Targeting tumor cell plasticity by combined inhibition of NOTCH and MAPK signaling in colon cancer
Authors: Eva Marina Schmidt, Sebastian Lamprecht, Cristina Blaj, Christian Schaaf, Stefan Krebs, Helmut Blum, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
Journal: The Journal of Experimental Medicine (2018)

In colorectal cancer, signaling pathways driving tumor progression are promising targets for systemic therapy. Besides WNT and MAPK signaling, activation of NOTCH signaling is found in most tumors. Here, we demonstrate that high NOTCH activity marks a distinct colon cancer cell subpopulation with low levels of WNT and MAPK activity and with a pronounced epithelial phenotype. Therapeutic targeting of MAPK signaling had limited effects on tumor growth and caused expansion of tumor cells with high NOTCH activity, whereas upon targeting NOTCH signaling, tumor cells with high MAPK activity prevailed. Lineage-tracing experiments indicated high plasticity between both tumor cell subpopulations as a mechanism for treatment resistance. Combined targeting of NOTCH and MAPK had superior therapeutic effects on colon cancer growth in vivo. These data demonstrate that tumor cells may evade systemic therapy through tumor cell plasticity and provide a new rationale for simultaneous targeting of different colon cancer cell subpopulations.
Multiple Factors Confounding Phylogenetic Detection of Selection on Codon Usage
Authors: Simon Laurin-Lemay, Hervé Philippe, Nicolas Rodrigue
Journal: Molecular Biology and Evolution (2018)

Detecting selection on codon usage (CU) is a difficult task, since CU can be shaped by both the mutational process and selective constraints operating at the DNA, RNA, and protein levels. Yang and Nielsen (2008) developed a test (which we call CUYN) for detecting selection on CU using two competing mutation-selection models of codon substitution. The null model assumes that CU is determined by the mutation bias alone, whereas the alternative model assumes that both mutation bias and/or selection act on CU. In applications on mammalian-scale alignments, the CUYN test detects selection on CU for numerous genes. This is surprising, given the small effective population size of mammals, and prompted us to use simulations to evaluate the robustness of the test to model violations. Simulations using a modest level of CpG hypermutability completely mislead the test, with 100% false positives. Surprisingly, a high level of false positives (56.1%) resulted simply from using the HKY mutation-level parameterization within the CUYN test on simulations conducted with a GTR mutation-level parameterization. Finally, by using a crude optimization procedure on a parameter controlling the CpG hypermutability rate, we find that this mutational property could explain a very large part of the observed mammalian CU. Altogether, our work emphasizes the need to evaluate the potential impact of model violations on statistical tests in the field of molecular phylogenetic analysis. The source code of the simulator and the mammalian genes used are available as a GitHub repository (https://github.com/Simonll/LikelihoodFreePhylogenetics.git).
Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine
Authors: David W. Dodick, Stephen D. Silberstein, Marcelo E. Bigal, Paul P. Yeung, Peter J. Goadsby, Tricia Blankenbiller, Melissa Grozinski-Wolff, Ronghua Yang, Yuju Ma, Ernesto Aycardi
Journal: JAMA (2018)

<h3>Importance</h3> Fremanezumab, a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, may be effective for treating episodic migraine. <h3>Objective</h3> To assess the efficacy of fremanezumab compared with placebo for prevention of episodic migraine with a monthly dosing regimen or a single higher dose. <h3>Design and Setting</h3> Randomized, double-blind, placebo-controlled, parallel-group trial conducted at 123 sites in 9 countries from March 23, 2016 (first patient randomized), to April 10, 2017, consisting of a screening visit, 28-day pretreatment period, 12-week treatment period, and final evaluation at week 12. <h3>Participants</h3> Study participants were aged 18 to 70 years with episodic migraine (6-14 headache days, with at least 4 migraine days, during 28-day pretreatment period). Patients who had previous treatment failure with 2 classes of migraine-preventive medication were excluded. <h3>Interventions</h3> Patients were randomized 1:1:1 to receive subcutaneous monthly dosing of fremanezumab (n = 290; 225 mg at baseline, week 4, and week 8); a single higher dose of fremanezumab, as intended to support a quarterly dose regimen (n = 291; 675 mg of fremanezumab at baseline; placebo at weeks 4 and 8); or placebo (n = 294; at baseline, week 4, and week 8). <h3>Main Outcomes and Measures</h3> The primary end point was mean change in mean number of monthly migraine days during the 12-week period after the first dose. <h3>Results</h3> Among 875 patients who were randomized (mean age, 41.8 [SD, 12.1] years; 742 women [85%]), 791 (90.4%) completed the trial. From baseline to 12 weeks, mean migraine days per month decreased from 8.9 days to 4.9 days in the fremanezumab monthly dosing group, from 9.2 days to 5.3 days in the fremanezumab single-higher-dose group, and from 9.1 days to 6.5 days in the placebo group. This resulted in a difference with monthly dosing vs placebo of –1.5 days (95% CI, –2.01 to –0.93 days;<i>P</i> &lt; .001) and with single higher dosing vs placebo of –1.3 days (95% CI, –1.79 to –0.72 days;<i>P</i> &lt; .001). The most common adverse events that led to discontinuation were injection site erythema (n = 3), injection site induration (n = 2), diarrhea (n = 2), anxiety (n = 2), and depression (n = 2). <h3>Conclusions and Relevance</h3> Among patients with episodic migraine in whom multiple medication classes had not previously failed, subcutaneous fremanezumab, compared with placebo, resulted in a statistically significant 1.3- to 1.5-day reduction in the mean number of monthly migraine days over a 12-week period. Further research is needed to assess effectiveness against other preventive medications and in patients in whom multiple preventive drug classes have failed and to determine long-term safety and efficacy. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02629861
Is depression screening in patients with acne critical?: reply from authors
Authors: I.A. Vallerand, R.T. Lewinson, L.M. Parsons, M.W. Lowerison, A.D. Frolkis, G.G. Kaplan, C. Barnabe, A.G.M. Bulloch, S.B. Patten
Journal: British Journal of Dermatology (2018)

Linked Articles:Unrue and Feldman. Br J Dermatol 2018; 179:226–227. Vallerand et al. Br J Dermatol 2018; 178:e194–5.
Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis
Authors: Kevin J. Frankowski, Chen Wang, Samarjit Patnaik, Frank J. Schoenen, Noel Southall, Dandan Li, Yaroslav Teper, Wei Sun, Irawati Kandela, Deqing Hu, Christopher Dextras, Zachary Knotts, Yansong Bian, John Norton, Steve Titus, Marzena A. Lewandowska, Yiping Wen, Katherine I. Farley, Lesley Mathews Griner, Jamey Sultan, Zhaojing Meng, Ming Zhou, Tomas Vilimas, Astin S. Powers, Serguei Kozlov, Kunio Nagashima, Humair S. Quadri, Min Fang, Charles Long, Ojus Khanolkar, Warren Chen, Jinsol Kang, Helen Huang, Eric Chow, Esthermanya Goldberg, Coral Feldman, Romi Xi, Hye Rim Kim, Gary Sahagian, Susan J. Baserga, Andrew Mazar, Marc Ferrer, Wei Zheng, Ali Shilatifard, Jeffrey Aubé, Udo Rudloff, Juan Jose Marugan, Sui Huang
Journal: Science Translational Medicine (2018)

A compound that reduces the prevalence of perinucleolar compartment in cancer cells inhibits metastasis in vivo.
PIAS3-mediated feedback loops promote chronic colitis-associated malignant transformation
Authors: Junting Ma, Yaping Yang, Yong Fu, Feilong Guo, Xiaoyi Zhang, Shuke Xiao, Weiming Zhu, Zhen Huang, Junfeng Zhang, Jiangning Chen
Journal: Theranostics (2018)

Rationale: Colitis-associated colorectal cancer (CAC) usually exhibits an accelerated disease progression, an increased resistance to therapeutic drugs and a higher mortality rate than sporadic colorectal cancer (CRC). PIAS3 is a member of the protein inhibitor of activated STAT (PIAS) family; however, little is known about the expression and biological functions of PIAS3 in CAC. The aim of our study was to investigate the biological mechanisms of PIAS3 in CAC. Methods: PIAS3 expression was examined in colon tissues of CAC/CRC patients and azoxymethane-dextran sulfate sodium (AOM-DSS)-induced mice. The role of PIAS3 was studied using a series of in vitro, in vivo and clinical approaches. Results: Downregulated PIAS3 expression, upregulated miR-18a expression and highly activated NF-κB and STAT3 were observed in colon tissues of CAC/CRC patients and AOM-DSS-induced mice. In vitro experiments revealed that PIAS3 significantly inhibited the activation of NF-κB and STAT3 and demonstrated that activated NF-κB and STAT3 transcriptionally regulated miR-18a level, and up-regulation of miR-18a expression led to defective PIAS3 expression. Moreover, PIAS3-mediated autoregulatory feedback loops (PIAS3/NF-κB/miR-18a and PIAS3/STAT3/miR-18a) were verified in vitro and were found to regulate cell proliferation. Additionally, modulation of the feedback loops via overexpression of PIAS3 or knockdown of miR-18a significantly inhibited cell proliferation in a mouse CRC xenograft model. Furthermore, upregulation of PIAS3 by intracolonic administration of PIAS3 lentivirus or anti-miR-18a lentivirus in AOM-DSS-induced mice led to dramatically reduced tumor sizes/numbers, whereas knockdown of PIAS3 in CAC mice significantly promoted tumor growth. Conclusion: Our data clearly show that PIAS3-mediated feedback loops control cell proliferation and function as robust driving forces for CAC progression. Targeting these highly activated feedback loops might offer promising therapeutic strategies for CAC.
Having small‐for‐gestational‐age infants was associated with maternal allergic features in the <scp>JECS</scp> birth cohort
Authors: M. Saito, K. Yamamoto‐Hanada, K. Pak, T. Ayabe, H. Mezawa, K. Ishitsuka, M. Konishi, L. Yang, K. Matsumoto, H. Saito, Y. Ohya
Journal: Allergy (2018)

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UK patients lose legal claim that DePuy metal-on-metal hip implant was “defective”
Authors: Clare Dyer
Journal: BMJ (2018)

More than 300 people who were fitted with a metal-on-metal hip implant that is no longer used have lost a UK group legal action against the US manufacturer.1

The claimants argued that DePuy International’s Pinnacle Ultamet hip replacement released metal debris into the surrounding tissue and was a defective product under the UK’s product liability law.

But at the High Court in London Mrs Justice Andrews ruled that the adverse reactions of some patients to metal wear debris was a known consequence of metal-on-metal hips and did not amount to a defect under the law. …