tbuckley/cabot-search huggingface dataset:
A molecular signature associated with prolonged survival in glioblastoma patients treated with regorafenib
Authors: Alessandra Santangelo, Marzia Rossato, Giuseppe Lombardi, Salvatore Benfatto, Denise Lavezzari, Gian Luca De Salvo, Stefano Indraccolo, Maria Cristina Dechecchi, Paola Prandini, Roberto Gambari, Chiara Scapoli, Gianfranco Di Gennaro, Mario Caccese, Marica Eoli, Roberta Rudà, Alba Ariela Brandes, Toni Ibrahim, Simona Rizzato, Ivan Lolli, Giuseppe Lippi, Massimo Delledonne, Vittorina Zagonel, Giulio Cabrini
Journal: Neuro-Oncology (2020)

Patients with glioblastoma (GBM) have a dramatically poor prognosis. The recent REGOMA trial suggested an overall survival (OS) benefit of regorafenib in recurrent GBM patients. Considering the extreme genetic heterogeneity of GBMs, we aimed to identify molecular biomarkers predictive of differential response to the drug.Total RNA was extracted from tumor samples of patients enrolled in the REGOMA trial. Genome-wide transcriptome and micro (mi)RNA profiles were associated with patients' OS and progression-free survival.In the first step, a set of 11 gene transcripts (HIF1A, CTSK, SLC2A1, KLHL12, CDKN1A, CA12, WDR1, CD53, CBR4, NIFK-AS1, RAB30-DT) and 10 miRNAs (miR-93-5p, miR-203a-3p, miR-17-5p, let-7c-3p, miR-101-3p, miR-3607-3p, miR-6516-3p, miR-301a-3p, miR-23b-3p, miR-222-3p) was filtered by comparing survival between regorafenib and lomustine arms. In the second step, a mini-signature of 2 gene transcripts (HIF1A, CDKN1A) and 3 miRNAs (miR-3607-3p, miR-301a-3p, miR-93-5p) identified a subgroup of patients showing prolonged survival after regorafenib administration (median OS range, 10.6-20.8 mo).The study provides evidence that a signature based on the expression of 5 biomarkers could help identify a subgroup of GBM patients exhibiting a striking survival advantage when treated with regorafenib. Although the presented results must be confirmed in larger replication cohorts, the study highlights potential biomarker options to help guide the clinical decision among regorafenib and other treatments in patients with relapsing GBM.
OP0027 Mechanical stress with silicon rod altered cartilaginous differentiatiation in pseudo-tendon sheath
Authors: Y Yutani, Y Yamano
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In a joint-like sliding surface, undifferentiated mesenchymal cells have been reported to show expression of cartilage-specific genes and cartilage-specific matrix production. <h3>Objectives</h3> In flexor tendon injury, tendon grafting is performed. When primary repair is impossible, a tendon sheath is constructed using a silicon rod. This area forms a sliding surface between the rod and the surrounding tissue, and cartilaginous differentiation is expected. <h3>Methods</h3> The subjects were 22- and 46-year-old male patients. The mean interval between the injuries and insertion of the silicon rod was 13 months, and the mean interval until the second operation after insertion of the silicon rod was 4 months. Tissue was obtained from the inner and outer layer of the newly formed tendon sheath tissue. Total RNA was extracted directly from each tissue. For quantitative RT-PCR, the non-radioisotope method was used. <h3>Results</h3> Although aggrecan was absent at the outer layer, the ratio of the expression of this gene to the expression of GAPDH was 0.15 at the inner layer of the newly formed tendon sheath. Gene expression of type II collagen was seen at a ratio of 0.28 at the inner layer, although it was also absent at the outer layer. On examining the gene expression of type I collagen and TGF-?A` were 0.49 and 0.17, respectively. CD44 and HAS-2 gene expression were also confirmed. <h3>Conclusion</h3> In the tissue evaluated in this study, the original tendon sheath had been destroyed, and new tissue formation was observed around the site of artificial tendon insertion. Generally, tissues in this region were considered just connective tissues. However, the newly synthsized tendon sheath showed expression of genes for aggrecan and type II collagen that were not observed in the surrounding tissue. These findings together with expression of TGF-?A` suggest alterations in the tissue differentiation function in this area. In the tissue of this area, mechanical stimulation may have played an important role in the differentiation of mesenchymal tissue.
Anti-TNF-associated immunogenicity: use a retroactive drug but a proactive approach
Authors: Ashish Srinivasan, Peter De Cruz, Daniel R van Langenberg
Journal: Gut (2020)

We read the study by Roblin et al with interest.1 Given that prior antitumour necrosis factor (anti-TNF) monotherapy failure is frequently associated with antibody development to a second anti-TNF within 24 months,2 it is our practice, to (re)introduce immunomodulator cotherapy with the second anti-TNF to reduce immunogenicity and improve treatment persistence.3 4 Roblin et al ’s findings support this concept, reinforcing the value of thiopurine cotherapy to reduce immunogenicity with the second anti-TNF following immune-mediated failure of first-line anti-TNF monotherapy. Moreover, they demonstrated that combination therapy was less frequently associated with clinical relapse, clinical failure and pharmacokinetic failure (ie, undetectable anti-TNF trough levels with high antidrug antibodies) than anti-TNF monotherapy. These data also imply a longer (24 months) duration of combination therapy may be required for those at increased risk of immunogenicity than previously (6–12 months) suggested.5 In retrospect, perhaps continuing combination therapy ab initio, particularly for infliximab where combination …
Evaluation of Primary Angle-Closure Glaucoma Susceptibility Loci for Estimating Angle Closure Disease Severity
Authors: Chang Liu, Monisha E. Nongpiur, Ching-Yu Cheng, Chiea-Chuen Khor, Marco Yu, Rahat Husain, Ching Lin Ho, Tina T. Wong, Pui Yi Boey, Shamira Perera, Tien Yin Wong, Eranga N. Vithana, Tin Aung
Journal: Ophthalmology (2020)
IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis
Authors: Rasmus Siersbæk, Valentina Scabia, Sankari Nagarajan, Igor Chernukhin, Evangelia K. Papachristou, Rebecca Broome, Simon J. Johnston, Stacey E.P. Joosten, Andrew R. Green, Sanjeev Kumar, Julia Jones, Soleilmane Omarjee, Ruben Alvarez-Fernandez, Silvia Glont, Sarah J. Aitken, Kamal Kishore, Danya Cheeseman, Emad A. Rakha, Clive D'Santos, Wilbert Zwart, Alasdair Russell, Cathrin Brisken, Jason S. Carroll
Journal: Cancer Cell (2020)
Evaluation of Use of Shorter Radiation Regimens for Breast and Prostate Cancer in the US, 2015-2017
Authors: Erin F. Gillespie, Kathryn R. Tringale, Peter B. Bach, Justin E. Bekelman
Journal: JAMA Network Open (2020)

This cross-sectional study examines the usage rates and trends of shorter vs longer radiation regimens for breast cancer and prostate cancer treatments in the US.
Continuation of Mosquito Surveillance and Control During Public Health Emergencies and Natural Disasters
Authors: C. Roxanne Connelly, Justin A. Gerding, Susan M. Jennings,, Andrew Ruiz, Roberto Barrera, Sue Partridge, C. Ben Beard
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Mosquitoborne disease outbreaks occur every year in the United States from one or more of the arboviral diseases dengue, West Nile, LaCrosse, Eastern equine encephalitis, and Zika (1). Public opinion communicated through traditional and social media and the Internet, competing public health and resource priorities, and local conditions can impede the ability of vector control organizations to prevent and respond to outbreaks of mosquitoborne disease. The Environmental Protection Agency (EPA) and CDC performed a coordinated review of the concerns and challenges associated with continuation of mosquito surveillance and control during public health emergencies and disasters. This report highlights the first joint recommendation from EPA and CDC. Mosquito surveillance and control should be maintained by state and local mosquito control organizations to the extent that local conditions and resources will allow during public health emergencies and natural disasters. Integrated pest management (IPM) is the best approach for mosquito control (2). IPM uses a combination of methods, including both physical and chemical means of control (3). For chemical means of control, CDC and EPA recommend the use of larvicides and adulticides following the EPA label. It is imperative that public health recommendations be followed to ensure the safety of the pesticide applicator and the public.
Individual red blood cell fetal hemoglobin quantification allows to determine protective thresholds in sickle cell disease
Authors: Nicolas Hebert, Marie Georgine Rakotoson, Gwellaouen Bodivit, Etienne Audureau, Laura Bencheikh, Laurent Kiger, Nadia Oubaya, Sadaf Pakdaman, Mehdi Sakka, Gaetana Di Liberto, Philippe Chadebech, Benoit Vingert, France Pirenne, Frédéric Galactéros, Marie Cambot, Pablo Bartolucci
Journal: American Journal of Hematology (2020)

Polymerization of the sickle hemoglobin (HbS) is a key determinant of sickle cell disease (SCD), an inherited blood disorder. Fetal hemoglobin (HbF) is a major modulator of the disease severity by both decreasing HbS intracellular concentration and inhibiting its polymerization. However, heterocellular distribution of HbF is common in SCD. For HbS polymerization inhibition, the hypothesis of an "HbF per red blood cell (HbF/RBC) threshold" requires accurate measurement of HbF in individual RBC. To date, HbF detection methods are limited to a qualitative measurement of RBC populations containing HbF - the F cells, which are variable. We developed an accurate method for HbF quantification in individual RBC. A linear association between mean HbF content and mean RBC fluorescence by flow cytometry, using an anti-Human-HbF antibody, was obtained from non-SCD subjects presenting homogeneous HbF distribution. This correlation was then used to measure HbF/RBC. Hydroxyurea (HU) improves SCD clinical manifestations, mainly through its ability to induce HbF synthesis. The HbF distribution was analyzed in 14 SCD patients before and during HU treatment. A significant decrease in RBC population containing less than 2 pg of HbF/RBC was observed. Therefore, we tested associations for %RBC above different HbF/RBC thresholds and showed a decrease in the pathognomonic vaso-occlusive crisis incidence from the threshold of 4 pg. This quantity was also correlated with the level of sickle RBC after in vitro deoxygenation. This new method allows the comparison of HbF/RBC distributions and could be a useful tool to characterize baseline patients HbF distribution and therapeutic response to HbF inducers.
STEEP mediates STING ER exit and activation of signaling
Authors: Bao-cun Zhang, Ramya Nandakumar, Line S. Reinert, Jinrong Huang, Anders Laustsen, Zong-liang Gao, Cheng-long Sun, Søren Beck Jensen, Anne Troldborg, Sonia Assil, Martin F. Berthelsen, Carsten Scavenius, Yan Zhang, Samuel J. Windross, David Olagnier, Thaneas Prabakaran, Chiranjeevi Bodda, Ryo Narita, Yujia Cai, Cong-gang Zhang, Harald Stenmark, Christine M. Doucet, Takeshi Noda, Zheng Guo, Raphaela Goldbach-Mansky, Rune Hartmann, Zhijian J. Chen, Jan J. Enghild, Rasmus O. Bak, Martin K. Thomsen, Søren R. Paludan
Journal: Nature Immunology (2020)
Gallbladder Carcinoma Presenting With Elbow Swelling
Authors: Shantanu S. Pande, Devendra Goyal, Zachariah Chowdhury, Ipsita Dhal, Abhishek Kumar Singh
Journal: Clinical Nuclear Medicine (2020)

Abstract Common presentation of primary gallbladder carcinoma is with abdominal pain, or it may be detected incidentally in postcholecystectomy specimen for cholelithiasis. Primary gallbladder carcinoma spreads to adjacent hepatic parenchyma and locoregional nodes. Lung is a common extra-abdominal site, with other sites being relatively rare. We report a case of primary gallbladder carcinoma, which presented with elbow swelling in the absence of locoregional nodal spread detected on whole-body 18 F-FDG PET/contrast-enhanced CT at initial evaluation.
Burkitt lymphoma in the modern era: real-world outcomes and prognostication across 30 US cancer centers
Authors: Andrew M. Evens, Alexey Danilov, Deepa Jagadeesh, Amy Sperling, Seo-Hyun Kim, Ryan Vaca, Catherine Wei, Daniel Rector, Suchitra Sundaram, Nishitha Reddy, Yong Lin, Umar Farooq, Christopher D'Angelo, David A. Bond, Stephanie Berg, Michael C. Churnetski, Amandeep Godara, Nadia Khan, Yun Kyong Choi, Maryam Yazdy, Emma Rabinovich, Gaurav Varma, Reem Karmali, Agrima Mian, Malvi Savani, Madelyn Burkart, Peter Martin, Albert Ren, Ayushi Chauhan, Catherine Diefenbach, Allandria Straker-Edwards, Andreas K. Klein, Kristie A. Blum, Kirsten Marie Boughan, Scott E. Smith, Brad M. Haverkos, Victor M. Orellana-Noia, Vaishalee P. Kenkre, Adam Zayac, Jeremy Ramdial, Seth M. Maliske, Narendranath Epperla, Parameswaran Venugopal, Tatyana A. Feldman, Stephen D. Smith, Andrzej Stadnik, Kevin A. David, Seema Naik, Izidore S. Lossos, Matthew A. Lunning, Paolo Caimi, Manali Kamdar, Neil Palmisiano, Veronika Bachanova, Craig A. Portell, Tycel Phillips, Adam J. Olszewski, Juan Pablo Alderuccio
Journal: Blood (2021)
Antiplatelet Treatment to Prevent Early Recurrent Stroke
Authors: Peter M. Rothwell
Journal: New England Journal of Medicine (2020)

Without urgent treatment, the risk of major stroke in the week after a transient ischemic attack (TIA) or minor stroke can be as high as 10%.1 Some studies have shown that immediate medical treatment with antiplatelet agents and statins, as well as blood-pressure control, reduces that risk by 70 to 80%,1,2 with the benefit attributable mainly to aspirin,3 but the residual 7-day risk of recurrent stroke is still 2 to 3%.4 Given the effectiveness of aspirin, might more intensive antiplatelet treatment with another drug or with dual antiplatelet treatment reduce this residual risk? No other single antiplatelet drug has been . . .
Response to: ‘Impact of COVID-19 pandemic on patients with SLE: results of a large multicentric survey from India’ by Goyal <i>et al</i>
Authors: Alexis Mathian, Zahir Amoura
Journal: Annals of the Rheumatic Diseases (2020)

Response to: 'Impact of COVID-19 pandemic on patients with SLE: results of a large multicentric survey from India' by Goyal et alWe thank Goyal et al for their interest in our study reporting on the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) in a case series of patients with systemic lupus erythematosus (SLE) under long-term treatment with hydroxychloroquine. 1 2 Goyal et al, on a series of 845 patients with SLE, reported symptoms compatible with COVID-19 in 17 (2.0%) and confirmed COVID-19 in only 1 (0.1%) of the patients.The very low frequency of COVID-19 in these patients reflects the low incidence of SARS-Cov-2 infection in the Indian population at the completion of their study.However, since then, the epidemic has unfortunately progressed and the number of deaths from COVID-19 in India has multiplied nearly 10-fold.Thus, the number of patients with SLE affected by COVID-19 is probably much higher now than that reported by Goyal et al at the beginning of the epidemic.The network of rheumatology centres that was created during this multicentric survey will make it possible to collect new information concerning the occurrence of SARS-CoV-2 infection in patients with SLE in India.However, we would like to insist on the necessity to use reliable markers to establish the diagnosis of COVID-19 such as viral detection by real-time reverse transcription-PCR analysis and/or the detection of anti-SARS-CoV-2 serum antibodies.In addition, a chest CT scan suggestive of SARS-CoV-2 pneumonia will also allow, in the context of a COVID-19 outbreak, to confirm the diagnosis of SARS-CoV-2 infection.Unfortunately, Goyal et al reported that only 2 out of 17 patients who reported fever, cough or shortness of breath were tested for infection with SARS-CoV-2.In the context of the low attack rate, observed at the beginning of the pandemic in India, the occurrence of this symptomatology is not synonymous with COVID-19 because infection with virus strains other than SARS-CoV-2 may cause similar, indistinguishable symptoms.We therefore insist on the use of the aforementioned diagnostic methods to improve the reliability of this type of study.[5][6]
THU0097 The discrepancy between mrna and protein expression of the tumour-suppressor gene maspin in synovial tissue might contribute to synovial hyperplasia in rheumatoid arthritis (ra)
Authors: J Schedel, E Jeisy Walder, B Simmen, BA Michel, RE Gay, S Gay
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> RA is a chronic disease characterised by tumour-like features such as synovial hyperplasia, invasive growth of the synovium and joint destruction. Maspin is a member of the serpin family of protease inhibitors with gene sequence similarities to plasminogen activator inhibitor. Maspin exhibits also tumour-suppressor activity by inhibiting cell motility, invasion and metastasis, and is down-regulated in breast and prostate cancer. <h3>Objectives</h3> We investigated the expression of maspin in RA synovial tissue and compared it with the expression in osteoarthritis (OA) and normal synovial tissues (NS). <h3>Methods</h3> The expression of maspin was determined in synovial tissue samples obtained during synovectomy or arthroplastic surgery. Using specific primers for maspin, a 237 bp fragment was amplified from cDNA obtained from cultured RA (6), OA (4) and normal (1) synovial fibroblasts (SF) by reverse transcription polymerase chain reaction (RT-PCR). In addition, mRNA expression levels were determined quantitatively by real-time PCR (TaqMan). Using non-radioactive <i>in situ</i> hybridization, mRNA expression of maspin was investigated using snap-frozen and paraffin sections. To identify the cell types expressing maspin, immunohistochemistry was performed on serial tissue sections using monoclonal antibodies against CD3 (T cells) and CD68 (macrophages). SDS-PAGE and Western blotting was performed using anti-maspin antibodies to evaluate the protein expression in total synovial tissue and in cultured synovial fibroblasts (3rd -4th passage). Protein from normal breast tissue was used as positive control. <h3>Results</h3> RT-PCR revealed expression of maspin in all cDNA samples from cultured synovial fibroblasts. By real-time PCR, maspin mRNA was found 2-fold decreased in RA-SF compared to OA-SF and 70-fold in comparison to NS-SF. Using <i>in situ</i> hybridization, maspin mRNA was expressed in RA as well as in OA and normal synovial tissue. Whereas in normal and OA samples, expression of maspin mRNA was restricted to synovial fibroblasts in the synovial lining and sublining, in RA, maspin could additionally be observed within perivascular infiltrates in mononuclear and multinucleated cells. Importantly, maspin transcripts were also found at sites of invasion into cartilage and bone. Interestingly, on the protein level, maspin could only be detected in normal breast tissue, but neither in RA synovial tissue nor in RA or OA synovial fibroblasts. <h3>Conclusion</h3> Since maspin is not expressed in RA-SF on the protein level, it is hypothesised that the lack of maspin could contribute to the hyperplasia of the synovial tissue in RA.
Alcoholism and affective disorder: clinical course of depressive symptoms
Authors: S A Brown, R K Inaba, J C Gillin, M A Schuckit, M A Stewart, M R Irwin
Journal: American Journal of Psychiatry (1995)

This study compared the severity of and the change in depressive symptoms among men with alcohol dependence, affective disorder, or both disorders during 4 weeks of inpatient treatment.After their primary and secondary psychiatric disorders were defined with the use of criteria based on chronology of symptoms, 54 unmedicated men entering treatment for alcohol dependence or affective disorder were assessed for 4 consecutive weeks with the Hamilton Depression Rating Scale.The findings indicate that the rate of remission of depressive symptoms was consistent with the primary diagnosis. Depressive symptoms remitted more rapidly among the men with primary alcoholism than among those with primary affective disorder. However, a minimum of 3 weeks of abstinence from alcohol appeared to be necessary to consistently differentiate the groups with dual diagnoses on the basis of their current depressive symptoms. Alcohol dependence occurring in conjunction with primary affective disorder did not intensify presenting depressive symptoms or retard the resolution of such symptoms.Diagnoses of alcohol dependence and affective disorder based on symptom chronology appear to have prognostic significance with respect to remission of depressive symptoms in men with both diagnoses. Depressive symptoms of dysphoric mood, dysfunctional cognitions, vegetative symptoms, and anxiety/agitation showed different rates and levels of remission across the primary diagnostic groups.
Decreased lymphatic HIF-2α accentuates lymphatic remodeling in lymphedema
Authors: Xinguo Jiang, Wen Tian, Eric J. Granucci, Allen B. Tu, Dongeon Kim, Petra Dahms, Shravani Pasupneti, Gongyong Peng, Yesl Kim, Amber H. Lim, F. Hernan Espinoza, Matthew Cribb, J. Brandon Dixon, Stanley G. Rockson, Gregg L. Semenza, Mark R. Nicolls
Journal: Journal of Clinical Investigation (2020)

Pathologic lymphatic remodeling in lymphedema evolves during periods of tissue inflammation and hypoxia through poorly defined processes. In human and mouse lymphedema, there is a significant increase of hypoxia inducible factor 1 α (HIF-1α), but a reduction of HIF-2α protein expression in lymphatic endothelial cells (LECs). We questioned whether dysregulated expression of these transcription factors contributes to disease pathogenesis and found that LEC-specific deletion of Hif2α exacerbated lymphedema pathology. Even without lymphatic vascular injury, the loss of LEC-specific Hif2α caused anatomic pathology and a functional decline in fetal and adult mice. These findings suggest that HIF-2α is an important mediator of lymphatic health. HIF-2α promoted protective phosphorylated TIE2 (p-TIE2) signaling in LECs, a process also replicated by upregulating TIE2 signaling through adenovirus-mediated angiopoietin-1 (Angpt1) gene therapy. Our study suggests that HIF-2α normally promotes healthy lymphatic homeostasis and raises the exciting possibility that restoring HIF-2α pathways in lymphedema could mitigate long-term pathology and disability.
心房細動患者におけるダビガトラン対ワルファリンの有効性と安全性 RE-LYトライアルにおける日本人集団のサブ解析
Authors: Hori Masatsugu, J Connolly Stuart, D Ezekowitz Michael, A Reilly Paul, Yusuf Salim, Wallentin Lars
Journal: Circulation (2011)
Coronary Revascularization Strategies
Authors: Steven E. Nissen, Faisal G. Bakaeen
Journal: JAMA (2020)

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