tbuckley/cabot-search huggingface dataset:
Attack Rates of Streptococcal Pharyngitis, Rheumatic Fever and Glomerulonephritis in the General Population
Authors: H. A. Valkenburg, W. R. O. Goslings, A. W. Bots, C. E. de Moor, J. C. Lorrier
Journal: New England Journal of Medicine (1963)

ALTHOUGH in the past twenty years the epidemiology of streptococcal infections has been studied extensively, only a few studies were conducted in the open civilian population. Most were done in more or less closed communities,1 , 2 in selected families3 , 4 or with children.5 6 7 8 In only one study was the population of a complete village followed clinically, bacteriologically and serologically9 during a period of seven years.The results of the attack rate of rheumatic fever and acute hemorrhagic glomerulonephritis in the population of a small town during a two-year period (May, 1959, through April, 1961) were presented in a preceding report.10 In . . .
Reactive Oxygen Species Play an Important Role in the Activation of Heat Shock Factor 1 in Ischemic-Reperfused Heart
Authors: JunichiroNishizawa, AkiraNakai, KatsuhikoMatsuda, MasashiKomeda, ToshihikoBan, KazuhiroNagata
Journal: Circulation (1999)

Background—The myocardial protective role of heat shock protein (HSP) has been demonstrated. Recently, we reported that ischemia/reperfusion induced a significant activation of heat shock factor (HSF) 1 and an accumulation of mRNA for HSP70 and HSP90. We examined the role of reactive oxygen species (ROSs) in the induction of stress response in the ischemic-reperfused heart. Methods and Results—Rat hearts were isolated and perfused with Krebs-Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element. Induction of mRNA for HSP70 and HSP90 was examined by Northern blot analysis. Repetitive ischemia/reperfusion, which causes recurrent bursts of free radical generation, resulted in burst activation of HSF1, and this burst activation was significantly reduced with either allopurinol 1 mmol/L (an inhibitor of xanthine oxidase) or catalase 2×105 U/L (a scavenger of H2O2). Significant activation of HSF1 was ob...
Preventing infectious complications when treating non‐malignant immune‐mediated hematologic disorders
Authors: Luis Malpica, David van Duin, Stephan Moll
Journal: American Journal of Hematology (2019)

Abstract Immunosuppressants, targeted antibody therapies, and surgical splenectomy are amongst the treatment choices for immune‐mediated non‐malignant hematologic disorders, with infection being the most common non‐hematological adverse event from these therapies. Corticosteroids are associated with a length‐of‐treatment and dose‐dependent risk for infection, including opportunistic infections. Screening and antimicrobial prophylaxis against tuberculosis, Strongyloides stercoralis , and Pneumocystis jirovecii pneumonia, are indicated in selected patients on steroids and with certain risk factors for infection. Rituximab is associated with hepatitis B virus reactivation. All patients planned to be started on rituximab should be screened for hepatitis B surface antigen and total core antibody, with antiviral prophylaxis given depending on test results. In eculizumab treated patients, immunization against meningococcal serogroups ACWY and B is recommended. In addition, some guidelines suggest antibiotic prophylaxis for the duration of eculizumab treatment. In splenectomized patients, counseling and immunization are cornerstones of infection prevention. Several federal and society guidelines about immunizations and prophylactic antimicrobial therapies for patients treated with various immunosuppressive agents exist and are summarized in this manuscript in a clinical‐focused table. In addition, management suggestions are made where no formal guidelines exist.
A circadian clock is essential for homeostasis of group 3 innate lymphoid cells in the gut
Authors: Fei Teng, Jeremy Goc, Lei Zhou, Coco Chu, Manish A. Shah, Gérard Eberl, Gregory F. Sonnenberg
Journal: Science Immunology (2019)

Group 3 innate lymphoid cells (ILC3s) critically orchestrate host-microbe interactions in the healthy mammalian intestine and become substantially impaired in the context of inflammatory bowel disease (IBD). However, the molecular pathways controlling the homeostasis of ILC3s remain incompletely defined. Here, we identify that intestinal ILC3s are highly enriched in expression of genes involved in the circadian clock and exhibit diurnal oscillations of these pathways in response to light cues. Classical ILC3 effector functions also exhibited diurnal oscillations, and lineage-specific deletion of BMAL1, a master regulator of the circadian clock, resulted in markedly reduced ILC3s selectively in the intestine. BMAL1-deficient ILC3s exhibit impaired expression of Nr1d1 and Per3, hyperactivation of RORγt-dependent target genes, and elevated proapoptotic pathways. Depletion of the microbiota with antibiotics partially reduced the hyperactivation of BMAL1-deficient ILC3s and restored cellular homeostasis in the intestine. Last, ILC3s isolated from the inflamed intestine of patients with IBD exhibit substantial alterations in expression of several circadian-related genes. Our results collectively define that circadian regulation is essential for the homeostasis of ILC3s in the presence of a complex intestinal microbiota and that this pathway is disrupted in the context of IBD.
A single arm, open label, phase II, multicenter study to assess the detection of the BRAF V600 mutation on cfDNA from plasma in patients with advanced melanoma
Authors: P. Rutkowski, P. Pauwels, J. Kerger, B. Jacobs, G.G. Maertens, V. Gadeyne, S. Liebert, B. Neyns
Journal: Annals of Oncology (2019)
Hyperoxia during cardiopulmonary bypass does not decrease cardiovascular complications following cardiac surgery: the CARDIOX randomized clinical trial
Authors: Osama Abou-Arab, Pierre Huette, Lucie Martineau, Clémence Beauvalot, Christophe Beyls, Estelle Josse, Gilles Touati, Olivier Bouchot, Belaïd Bouhemad, Momar Diouf, Emmanuel Lorne, Pierre-Grégoire Guinot
Journal: Intensive Care Medicine (2019)
Methotrexate enhances ALA-mediated photodynamic therapy in prostate cancer cells.
Authors: Sanjay Anand, Bernhard J. Ortel, Alok K. Sinha, Tayyaba Hasan, Edward V. Maytin
Journal: Cancer Research (2004)

2011  BACKGROUND: Photodynamic therapy (PDT) is an emerging binary treatment for cancer. As most non-surgical cancer therapies are used in combination regimens, we have evaluated the combination of methotrexate (MTX) with PDT using aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) in prostate cancer cells. Induction of differentiation enhances the efficacy of photodynamic treatment in several cell lines (Ortel et al., Brit J. Cancer 77:1744-1751, 1998). Because differentiation is associated with growth arrest, we have explored the use of chemotherapy-induced transitory growth arrest as a way to enhance ALA-PDT. Because the accumulation of photoactive porphyrins in cells after ALA administration occurs through upregulation of the coproporphyrinogen oxidase (CPO), we have also begun detailed studies on the regulation of this enzyme during binary treatments, such as MTX therapy. METHODS: MTX was used in combination with ALA-dependent PDT in the human prostate cancer cell line LNCaP, and in mouse BALB/MK keratinocytes. Cells were exposed to 1mg/L MTX for 72 hours. MTX was removed and cells were incubated with ALA for 4 hours, followed immediately by irradiation with 514 nm light. Survival was assessed by MTT and clonogenic assays. To investigate changes in expression of the CPO gene, 1 kb of the mouse CPO promoter was cloned upstream of the luciferase (LUC) gene, and the CPO-LUC reporter construct was transfected into cells along with expression constructs for a number of different isoforms of the C/EBP gene family. Expression of the C/EBP proteins was confirmed by Western blot. RESULTS: MTX treatment of cells resulted in growth arrest, and in expression of GADD153 (a C/EBP family member associated with ER stress). Subsequent exposure to ALA for 4 hours resulted in a 4.3 ± 1.2-fold increase in the rate of PpIX formation in LNCaP cells. Consequently, cytotoxicity at 24 hours after light exposure was enhanced, and long-term survival as quantified by colony formation was reduced with MTX pretreatment. The interaction of MTX and ALA was sequence dependent, i.e., LNCaP cells exposed first to ALA-PDT and later to methotrexate, showed no reduction in long-term survival . Thus, enhancement of cytotoxicity by MTX in the combined regimen is due to the increase in PpIX formation. In studies using the CPO-LUC reporter, cotransfection with all C/EBPbeta isoforms (LAP*, LAP, and LIP) and with GADD153 led to CPO promoter activation, but the largest induction was seen consistently with GADD153. Interestingly, treatment of cells with MTX led to upregulation of GADD153 protein. GADD153 may thus play a role in the activation of CPO expression, elevation of PpIX levels, and enhancement of ALA-PDT efficacy. CONCLUSION: The combination of short-term chemotherapy and subsequent ALA-PDT may help reduce dose-related toxicity of either component and thus improve existing PDT regimens for cancer treatment.
A key role for the novel coronary artery disease gene JCAD in atherosclerosis via shear stress mechanotransduction
Authors: Gillian Douglas, Vedanta Mehta, Ayman Al Haj Zen, Ioannis Akoumianakis, Anuj Goel, Victoria S Rashbrook, Lucy Trelfa, Lucy Donovan, Edward Drydale, Surawee Chuaiphichai, Charalambos Antoniades, Hugh Watkins, Theodosios Kyriakou, Ellie Tzima, Keith M Channon
Journal: Cardiovascular Research (2019)

Abstract Aims Genome-wide association studies (GWAS) have consistently identified an association between coronary artery disease (CAD) and a locus on chromosome 10 containing a single gene, JCAD (formerly KIAA1462). However, little is known about the mechanism by which JCAD could influence the development of atherosclerosis. Methods and results Vascular function was quantified in subjects with CAD by flow-mediated dilatation (FMD) and vasorelaxation responses in isolated blood vessel segments. The JCAD risk allele identified by GWAS was associated with reduced FMD and reduced endothelial-dependent relaxations. To study the impact of loss of Jcad on atherosclerosis, Jcad−/− mice were crossed to an ApoE−/− background and fed a high-fat diet from 6 to16 weeks of age. Loss of Jcad did not affect blood pressure or heart rate. However, Jcad−/−ApoE−/− mice developed significantly less atherosclerosis in the aortic root and the inner curvature of the aortic arch. En face analysis revealed a striking reduction in pro-inflammatory adhesion molecules at sites of disturbed flow on the endothelial cell layer of Jcad−/− mice. Loss of Jcad lead to a reduced recovery perfusion in response to hind limb ischaemia, a model of altered in vivo flow. Knock down of JCAD using siRNA in primary human aortic endothelial cells significantly reduced the response to acute onset of flow, as evidenced by reduced phosphorylation of NF-КB, eNOS, and Akt. Conclusion The novel CAD gene JCAD promotes atherosclerotic plaque formation via a role in the endothelial cell shear stress mechanotransduction pathway.
Effect of community-initiated kangaroo mother care on survival of infants with low birthweight: a randomised controlled trial
Authors: Sarmila Mazumder, Sunita Taneja, Brinda Dube, Kiran Bhatia, Runa Ghosh, Medha Shekhar, Bireshwar Sinha, Rajiv Bahl, Jose Martines, Maharaj Kishan Bhan, Halvor Sommerfelt, Nita Bhandari
Journal: The Lancet (2019)
Graft Failure Post Allogeneic Stem Cell Transplant: Conditioning Regimen Improves Engraftment and Survival
Authors: Lohith Gowda, Rima M. Saliba, Mithun Vinod Shah, Gabriela Rondon, Irfa Badar, Amanda L. Olson, Stefan O. Ciurea, Partow Kebriaei, Samer A. Srour, Simrit Parmar, Yago Nieto, Sairah Ahmed, Rohtesh S. Mehta, Gheath Alatrash, David Costa Marin, Borje S Andersson, Betul Oran, Qaiser Bashir, Muzaffar H. Qazilbash, Chitra Hosing, Issa F. Khouri, Amin M. Alousi, Paolo Anderlini, Elizabeth J Shpall, Katy Rezvani, Richard E Champlin, Uday Popat
Journal: Blood (2017)
Patient reported outcomes during immunotherapy: Symptom burden in daily clinical practice
Authors: J.J. Koldenhof, E.G. Verberne, R.J. Verheijden, E. Tonk, F.H. van der Baan, A. van Lindert, J. van der Stap, S.C. Teunissen, P.O. Witteveen, K.P.M. Suijkerbuijk
Journal: Annals of Oncology (2019)
A phase II trial of preoperative chemoradiotherapy and pembrolizumab for locally advanced esophageal squamous cell carcinoma (ESCC)
Authors: S. Lee, B.C. Ahn, S.Y. Park, D.J. Kim, C.G. Lee, J. Cho, J.H. Kim, H.R. Kim, Y.-H. Kim, S.R. Park, Y.J. Chun, M.H. Hong, H.R. Kim, B. Cho
Journal: Annals of Oncology (2019)
Improving patient selection for immuno-oncology phase I trials: An external validation of five prognostic scores at Claudius Regaud Institute of Toulouse, Oncopôle (IUCT-O)
Authors: G Al Darazi, E. Martin, J.-P. Delord, I. Korakis, S. Betrian, M. Poublanc, F. Ollivier, T. Filleron, C.A. Gomez-Roca
Journal: Annals of Oncology (2019)
Trilaciclib improves overall survival when given with gemcitabine/carboplatin (GC) in patients with metastatic triple negative breast cancer (mTNBC) in a randomized phase II trial
Authors: J. O’Shaughnessy, G.S. Wright, A. Thummala, M. Danso, L.S. Popovic, T. Pluard, H.S. Han, Z. Vojnovic, N. Vasev, L. Ma, D.A. Richards, S. Wilks, D.M. Milenkovic, J.A. Sorrentino, Z. Yang, J.K. Horton, A.R. Tan
Journal: Annals of Oncology (2019)
Comparison of platforms for determining tumour mutational burden (TMB) in patients with non-small cell lung cancer (NSCLC)
Authors: J. Baden, C. Zhao, J. Pratt, S. Kirov, S. Pant, A. Seminara, G. Green, S. Bilke, I. Deras, D.A. Fabrizio, T. Pawlowski
Journal: Annals of Oncology (2019)
Diagnostic value of digital multiplexed detection of single nucleotide variants in pancreatic cancer specimens collected by endoscopic ultrasound fine-needle aspiration
Authors: I.M. Cazacu, A. Semaan, B.M. Stephens, D.B. Swartzlander, P.A. Guerrero, B.S. Singh, C.V. Lungulescu, S. Raileanu, M.M. Danciulescu, S. Roy-Chowdhuri, A. Maitra, A. Saftoiu, M.S. Bhutani
Journal: Annals of Oncology (2019)
Bone mineral density in virologically suppressed people aged 60 years or older with HIV-1 switching from a regimen containing tenofovir disoproxil fumarate to an elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide single-tablet regimen: a multicentre, open-label, phase 3b, randomised trial
Authors: Franco Maggiolo, Giuliano Rizzardini, François Raffi, Federico Pulido, Maria Gracia Mateo-Garcia, Jean-Michel Molina, Edmund Ong, Yongwu Shao, David Piontkowsky, Moupali Das, Ian McNicholl, Richard Haubrich
Journal: The Lancet HIV (2019)
Circulating biomarkers and risk of immune-related adverse events (irAEs) in patients (pts) with advanced non-small cell lung cancer (aNSCLC) and metastatic melanoma (mMel)
Authors: A. Pavan, L. Calvetti, A. Dal Maso, A. Fabozzi, L. Piccin, V. Chiarion-Sileni, G. Pasello, G. Aprile, V. Guarneri, P.F. Conte, L. Bonanno
Journal: Annals of Oncology (2019)
Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy
Authors: Sanjeev Sethi, Hanna Debiec, Benjamin Madden, M. Cristine Charlesworth, Johann Morelle, LouAnn Gross, Aishwarya Ravindran, David Buob, Michel Jadoul, Fernando C. Fervenza, Pierre Ronco
Journal: Kidney International (2019)

Membranous nephropathy is characterized by deposition of immune complexes along the glomerular basement membrane. PLA2R and THSD7A are target antigens in 70% and 1-5% of primary membranous nephropathy cases, respectively. In the remaining cases, the target antigen is unknown. Here, laser microdissection of glomeruli followed by mass spectrometry was used to identify novel antigen(s) in PLA2R-negative membranous nephropathy. An initial pilot mass spectrometry study in 35 cases of PLA2R-negative membranous nephropathy showed high spectral counts for neural tissue encoding protein with EGF-like repeats, NELL-1, in six cases. Mass spectrometry failed to detect NELL-1 in 23 PLA2R-associated membranous nephropathy and 88 controls. NELL-1 was localized by immunohistochemistry, which showed bright granular glomerular basement membrane staining for NELL-1 in all six cases. Next, an additional 23 NELL-1 positive cases of membranous nephropathy were identified by immunohistochemistry in a discovery cohort of 91 PLA2R-negative membranous nephropathy cases, 14 were confirmed by mass spectrometry. Thus, 29 of 126 PLA2R-negative cases were positive for NELL-1. PLA2R-associated membranous nephropathy and controls stained negative for NELL-1. We then identified five NELL-1 positive cases of membranous nephropathy out of 84 PLA2R and THSD7A-negative cases in two validation cohorts from France and Belgium. By confocal microscopy, both IgG and NELL-1 co-localized to the glomerular basement membrane. Western blot analysis showed reactivity to NELL-1 in five available sera, but no reactivity in control sera. Clinical and biopsy findings of NELL-1 positive membranous nephropathy showed features of primary membranous nephropathy. Thus, a subset of membranous nephropathy is associated with accumulation and co-localization of NELL-1 and IgG along the glomerular basement membrane, and with anti-NELL-1 antibodies in the serum. Hence, NELL-1 defines a distinct type of primary membranous nephropathy.
Plasmatic CXCL8 is a marker for TGFß-activated kinase 1 (TAK1) activation which may predict resistance to nanoliposomal irinotecan (nal-IRI) in gemcitabine-refractory pancreatic cancer (PC) patients
Authors: V. Merz, C. Zecchetto, R. Santoro, F. Simionato, G. Piro, F. Sabbadini, A. Cavaliere, S. Casalino, A. Auriemma, D. Melisi
Journal: Annals of Oncology (2019)
Abstract 3719: Using the Framingham Risk Score to Select Low-risk Men for CAC Screening
Authors: Allen J Taylor, Irwin M Feuerstein, Holly Wu, Jody Bindeman, Kelly Bauer, Carole Byrd, Patrick G O’Malley
Journal: Circulation (2007)

Background Although coronary artery calcium (CAC) is predictive of future CHD, screening for CAC in low risk populations is controversial. Criteria are needed to narrow the screening population to those in whom CAC measurement is most efficient (vs. unselected screening). In this analysis, we report the relationship between CAC and CHD outcomes across Framingham risk score (FRS) subgroups to test whether there is a differential relationship between CAC and outcomes across baseline risk. Methods In 1634 unselected male volunteers (mean age 42, mean 10 year CHD FRS 4.6%, CAC prevalence 22.4%), we evaluated the independent relationship between CAC and incident CHD over 5.6 years including hard events (hospitalized unstable angina, myocardial infarction and CHD death) and coronary revascularization. The cohort was stratified into tertiles of FRS to explore the relationship between CAC and CHD outcomes. Results FRS tertile cutpoints were 0 –3%, 3–5%, and &gt;5% 10 year CHD risk. Over a mean 5.6 years ± 1.5 year of follow-up (range: 1.0 to 8.3 years), there were 22 total CHD events, including 14 hard events and 8 revascularizations. The majority of events occurred in the highest FRS tertile (n = 14), versus the middle (n= 6) and lowest risk tertiles (n=2; P = 0.005). Only in the highest FRS tertile was there a significant relationship between CAC and CHD outcomes. Conclusion Among asymptomatic low risk men, the presence of CAC demonstrates substantial discriminating power in predicting events, but appears to be most clinically useful when the 10-year FRS exceeds approximately 5%. If screening with CAC is pursued among low risk men, it should be preceded by a FRS and restricted to those with scores &gt;5%.
The Outcome of TGFβ Antagonism in Metastatic Breast Cancer Models <i>In Vivo</i> Reflects a Complex Balance between Tumor-Suppressive and Proprogression Activities of TGFβ
Authors: Yuan Yang, Howard H. Yang, Binwu Tang, Alex Man Lai Wu, Kathleen C. Flanders, Nellie Moshkovich, Douglas S. Weinberg, Michael A. Welsh, Jia Weng, Humberto J. Ochoa, Tiffany Y. Hu, Michelle A. Herrmann, Jinqiu Chen, Elijah F. Edmondson, R. Mark Simpson, Fang Liu, Huaitian Liu, Maxwell P. Lee, Lalage M. Wakefield
Journal: Clinical Cancer Research (2019)

Abstract Purpose: TGFβs are overexpressed in many advanced cancers and promote cancer progression through mechanisms that include suppression of immunosurveillance. Multiple strategies to antagonize the TGFβ pathway are in early-phase oncology trials. However, TGFβs also have tumor-suppressive activities early in tumorigenesis, and the extent to which these might be retained in advanced disease has not been fully explored. Experimental Design: A panel of 12 immunocompetent mouse allograft models of metastatic breast cancer was tested for the effect of neutralizing anti-TGFβ antibodies on lung metastatic burden. Extensive correlative biology analyses were performed to assess potential predictive biomarkers and probe underlying mechanisms. Results: Heterogeneous responses to anti-TGFβ treatment were observed, with 5 of 12 models (42%) showing suppression of metastasis, 4 of 12 (33%) showing no response, and 3 of 12 (25%) showing an undesirable stimulation (up to 9-fold) of metastasis. Inhibition of metastasis was immune-dependent, whereas stimulation of metastasis was immune-independent and targeted the tumor cell compartment, potentially affecting the cancer stem cell. Thus, the integrated outcome of TGFβ antagonism depends on a complex balance between enhancing effective antitumor immunity and disrupting persistent tumor-suppressive effects of TGFβ on the tumor cell. Applying transcriptomic signatures derived from treatment-naïve mouse primary tumors to human breast cancer datasets suggested that patients with breast cancer with high-grade, estrogen receptor–negative disease are most likely to benefit from anti-TGFβ therapy. Conclusions: Contrary to dogma, tumor-suppressive responses to TGFβ are retained in some advanced metastatic tumors. Safe deployment of TGFβ antagonists in the clinic will require good predictive biomarkers.
Characterization of lung tumourspheres reveals cancer stem-like cells potential targets and prognostic markers in non-small cell lung cancer
Authors: A. Herreros Pomares, E. Jantus-Lewintre, S. Calabuig-Fariñas, J.D. de-Maya-Girones, R. Lucas, A. Blasco, R. Guijarro, M. Martorell, E. Escorihuela, S. Alonso, M.D. Chiara, E. Duréndez, C. Gandia, R. Sirera, R. Farràs, C. Camps
Journal: Annals of Oncology (2019)
The relationship between naldemedine administration and the maximum dose of oral opioids
Authors: S. Kajiura, S. Chikaoka, T. Yokota, A. Kadota, S. Fukai, T. Matsushita, N. Hayashi, Y. Yagi, N. Ryu, H. Horikawa, K. Takemura, A. Furuichi, K. Nakajima, I. Moto, S. Nanjyo, H. Mihara, T. Ando, N. Murakami, I. Yasuda, R. Hayashi
Journal: Annals of Oncology (2019)