tbuckley/cabot-search huggingface dataset:
Depression, immunity, and survival in patients diagnosed with hepatobiliary carcinoma
Authors: J. L. Steel, D. A. Geller, M. C. Olek, B. I. Carr
Journal: Journal of Clinical Oncology (2006)

18525 Background: Depression has been found to be associated with increased morbidity and mortality in healthy adults. The prevalence of depression in patients diagnosed with cancer, and in particular hepatobiliary carcinoma (HBC), is significantly higher than the general population. The aims of the present study were to: (1) examine the prevalence of depressive symptoms in patients with HBC, (2) test the relationship between depressive symptoms and survival, and (3) begin to explore underlying mechanisms that explain the relationship between depression and survival in patients with HBC. Methods: 101 patients diagnosed with HBC were administered a battery of questionnaires which included the Center for Epidemiological Studies-Depression (CES-D) questionnaire. Disease-specific data was gathered from medical charts and survival was measured from the date of diagnosis to death. Immune markers (NK cell, IL-4 and 5, TNF, and IFN) were collected in 24 patients. Results: At diagnosis, 39% of the sample reported a score of 16 or greater (clinical range). Using Cox Regression, demographic (age, gender, ethnicity) and disease specific variables (diagnosis, treatment, hepatitis, cirrhosis, tumor location, tumor number, tumor size, vascularity of lesion, and portal vein invasion) variables, as well as CES-D score at diagnosis were analyzed. CES-D scores &gt;16 [Wald = 4.0, p = 0.05] and portal vein invasion (PVI) [Wald = 9.0, p = 0.003] significantly predicted survival. Using Kaplan Meier Survival analysis (Breslow test) and stratifying for PVI, a trend was found [Chi-Square = 3.1, p = 0.08] in which patients with PVI and CES-D scores &gt;16, survived 7.4 months whereas patients with CES-D scores &lt;16 survival 13 months. Patients without PVI and CES-D scores &gt;16 survived 18.2 months whereas those with CES-D scores &lt;16 survived 24.7 months. In a sample of 24 patients, those who reported CES-D scores &gt;16 had significantly lower Natural Killer cell numbers than patients with CES-D scores &lt;16 while covarying age, gender, stress, social support, and coping style [F(1,21) = 9.39, p = 0.003]. Conclusions: Depression may be an important prognostic factor for patients diagnosed with HBC. No significant financial relationships to disclose.
Short-term outcomes of COVID-19 and risk factors for progression
Authors: Li Long, Xiansheng Zeng, Xu Zhang, Wei Xiao, E Guo, Wenzhi Zhan, Xuejiao Yang, Chunyan Li, Caiyun Wu, Tingting Xu, Chen Zhan, Yuehan Chen, Mei Jiang, Nanshan Zhong, Kefang Lai
Journal: European Respiratory Journal (2020)

<b>With a median (IQR</b><b>) follow-up time of 24.0 (17.5–30.0) days, progression occurred in 19.6% moderate, 27.8% severe and 66.7% critical COVID-19. Neutrophil-to-lymphocyte ratio ≥2.973, age ≥50 years, male sex and comorbidity were associated with progression.</b>https://bit.ly/3crsJr0
Structural Phylogenetics with Confidence
Authors: Ashar J Malik, Anthony M Poole, Jane R Allison
Journal: Molecular Biology and Evolution (2020)

Abstract For evaluating the deepest evolutionary relationships among proteins, sequence similarity is too low for application of sequence-based homology search or phylogenetic methods. In such cases, comparison of protein structures, which are often better conserved than sequences, may provide an alternative means of uncovering deep evolutionary signal. Although major protein structure databases such as SCOP and CATH hierarchically group protein structures, they do not describe the specific evolutionary relationships within a hierarchical level. Structural phylogenies have the potential to fill this gap. However, it is difficult to assess evolutionary relationships derived from structural phylogenies without some means of assessing confidence in such trees. We therefore address two shortcomings in the application of structural data to deep phylogeny. First, we examine whether phylogenies derived from pairwise structural comparisons are sensitive to differences in protein length and shape. We find that structural phylogenetics is best employed where structures have very similar lengths, and that shape fluctuations generated during molecular dynamics simulations impact pairwise comparisons, but not so drastically as to eliminate evolutionary signal. Second, we address the absence of statistical support for structural phylogeny. We present a method for assessing confidence in a structural phylogeny using shape fluctuations generated via molecular dynamics or Monte Carlo simulations of proteins. Our approach will aid the evolutionary reconstruction of relationships across structurally defined protein superfamilies. With the Protein Data Bank now containing in excess of 158,000 entries (December 2019), we predict that structural phylogenetics will become a useful tool for ordering the protein universe.
Exisulind Selectively Induces Apoptosis Via C-Jun Kinase Activation in MDS and sAML/MDS.
Authors: Akos Czibere, Wolf C. Prall, Sabine Knipp, Andrea Kuendgen, Luiz F. Zerbini, Ulrich Germing, Rainer Haas, Towia A. Libermann, Norbert Gattermann, Manuel Aivado
Journal: Blood (2005)
Identification of a Second Acute Promyelocytic Leukemia (APL) Patient with the STAT5b-RARα Fusion Gene among PML-RARα-Negative Eastern Cooperative Oncology Group (ECOG) APL Protocol Registrants.
Authors: Robert E. Gallagher, Serena Mak, Elisabeth Paietta, Brenda Cooper, W. Christopher Ehmann, Martin S. Tallman
Journal: Blood (2004)
Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High‐Risk Lesions
Authors: George A. Karpouzas, Sarah R. Ormseth, Elizabeth Hernandez, Matthew J. Budoff
Journal: Arthritis & Rheumatology (2020)

Objective To evaluate whether biologic disease‐modifying antirheumatic drugs ( DMARD s) decrease cardiovascular disease ( CVD ) risk in rheumatoid arthritis ( RA ) and whether biologic DMARD s might have a beneficial effect on coronary plaque formation or progression. Methods In this single‐center observational cohort study, 150 patients underwent computed tomographic angiography for evaluation of coronary atherosclerosis (total, noncalcified, mixed/calcified, and low‐attenuation plaque); 101 had repeat assessments within a mean ± SD of 6.9 ± 0.3 years to evaluate plaque progression. All CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and hospitalization for heart failure. The Framingham‐D'Agostino score was used to assess cardiovascular risk. The segment stenosis score was used to measure plaque burden. Odds ratios ( OR s) with 95% confidence intervals (95% CI s) were calculated. Results After adjustment for the segment stenosis score, the Framingham‐D'Agostino score , and time‐varying Disease Activity Score in 28 joints using the C‐reactive protein level using marginal structural models, current biologic DMARD use was associated with lower long‐term CVD risk ( OR 0.15 [95% CI 0.04–0.60]). Noncalcified and low‐attenuation plaque presence moderated the effect of biologic DMARD s on CVD risk; specifically, biologic DMARD use was associated with lower CVD risk in patients with noncalcified or low‐attenuation plaque at baseline ( OR 0.21 [95% CI 0.04–0.99] and OR 0.08 [95% CI 0.01–0.70], respectively), but not in those without noncalcified or low‐attenuation plaque. Per‐segment plaque progression analyses showed that biologic DMARD exposure was associated with transition of noncalcified to mixed/calcified plaque ( OR 4.00 [95% CI 1.05–15.32]). Biologic DMARD exposure predicted a lower likelihood of new plaque forming in segments without plaque among patients without mixed/calcified plaque in other coronary segments ( OR 0.40 [95% CI 0.17–0.93]), but not among those with calcification. Biologic DMARD treatment also predicted low‐attenuation plaque loss ( P = 0.042). Conclusion Our findings indicate that in RA , biologic DMARD use is associated with reduced CVD risk, protective calcification of noncalcified lesions, and lower likelihood of new plaque formation in patients with early atherosclerosis.
Abstract IA09: The particulars of circulars: Novel RNAs from oncogenic herpesviruses
Authors: Yuan Chang
Journal: Cancer Research (2020)

Abstract Circular RNAs (circRNA) are formed by backsplicing of linear RNA. Due to their covalently joined cyclized nature, circRNAs are resistant to exonucleases and therefore comparatively more stable than their linear counterparts. Kaposi sarcoma-associated herpesvirus (KSHV/HHV8) and Epstein-Barr virus (EBV/HHV4) have recently been found by RNA sequencing to generate circular RNAs (circRNAs) in infected tissues and cell lines. These molecules represent a novel class of viral RNA that may have a more sustained functional role than linear transcripts. Initial characterization shows that circRNAs are expressed in infection-associated diseases and can be regulated depending on virus life cycle—although the quantity, localization, cell type, and viral life cycle expression of individual circRNAs vary considerably. Some viral circRNAs are incorporated into viral particles for preformed delivery, suggesting a potential function in early infection. Citation Format: Yuan Chang. The particulars of circulars: Novel RNAs from oncogenic herpesviruses [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA09.
Effect of Cyclosporine A and Estrogen-Receptor Inhibitor on the Reversion of Multidrug Resistance of K562/A02 Line.
Authors: Bao-An Chen, Wen Bao, Feng Gao, Jian Cheng, Chong Gao, Jia-Hua Ding, Yun-Yu Sun, Jun Wang, Gang Zhao, Ning-Na Chen, Fei Fei
Journal: Blood (2006)
In patients with SBP ≥ 130 mm Hg and CV risk, intensive vs standard BP control did not increase fear of falling
Authors: Alena Shantsila, Gregory Y.H. Lip
Journal: Annals of Internal Medicine (2020)

Source Citation Berlowitz DR, Foy C, Conroy M, et al. Impact of intensive blood pressure therapy on concern about falling: longitudinal results from the Systolic Blood Pressure Intervention Trial (SPRINT). J Am Geriatr Soc. 2019. [Epub ahead of print]. 31778222
Preclinical Activity of Novel BET Protein Proteolysis Targeting Chimeras (BETP-PROTACs) and Their Combination with Venetoclax or CDK4/6 Inhibitor Against Human Mantle Cell Lymphoma (MCL) Cells
Authors: Baohua Sun, Warren Fiskus, Kanak Raina, Yimin Qian, Andrew Crew, Dyana T. Saenz, Christopher Peter Mill, Agnieszka J Nowak, David N Saenz, Craig M Crews, Kapil N. Bhalla
Journal: Blood (2017)
Preoperative oral antibiotics and surgical-site infections in colon surgery (ORALEV): a multicentre, single-blind, pragmatic, randomised controlled trial
Authors: Eloy Espin Basany, Alejandro Solís-Peña, Gianluca Pellino, Esther Kreisler, Doménico Fraccalvieri, Manuel Muinelo-Lorenzo, Olga Maseda-Díaz, José María García-González, Marta Santamaría-Olabarrieta, Antonio Codina-Cazador, Sebastiano Biondo
Journal: The Lancet. Gastroenterology & hepatology (2020)
Pleuroparenchymal fibroelastosis in systemic sclerosis: prevalence and prognostic impact
Authors: Martina Bonifazi, Nicola Sverzellati, Eva Negri, Joseph Jacob, Ryoko Egashira, Joanna Moser, Sara Piciucchi, Federico Mei, Angelo De Lauretis, Dina Visca, Nicole Goh, Matteo Bonini, Laura Cirilli, Carlo La Vecchia, Felix Chua, Vasileios Kouranos, George Margaritopoulos, Maria Kokosi, Toby M. Maher, Stefano Gasparini, Armando Gabrielli, Athol U. Wells, Elisabetta A. Renzoni
Journal: European Respiratory Journal (2020)

Interstitial lung disease (ILD) in systemic sclerosis (SSc) is a major cause of morbidity and mortality, mostly presenting as non-specific interstitial pneumonia. Little is known about the prevalence of pleuroparenchymal fibroelastosis (PPFE), a specific entity affecting the visceral pleura and subpleural parenchyma. We set out to estimate PPFE prevalence in two large cohorts of SSc patients and to assess its impact on survival and functional decline. A total of 359 SSc patients, derived from two referral centres in two different countries (UK and Italy), were included. The first available high-resolution computed tomography scan was independently evaluated by two radiologists blind to clinical information, to quantify ILD extent, freestanding bronchial abnormalities, and lobar percentage involvement of PPFE on a four-point categorical scale. Discordant scores were adjudicated by a third scorer. PPFE extent was further classified as limited (≤2/18) or extensive (&gt;2/18). Results were evaluated against functional decline and mortality. The overall prevalence of PPFE in the combined SSc population was 18% (11% with extensive PPFE), with no substantial difference between the two cohorts. PPFE was significantly linked to free-standing bronchial abnormalities (61% versus 25% in PPFE versus no PPFE; p&lt;0.0001) and to worse survival, independently of ILD severity or short-term lung function changes (HR 1.89, 95% CI 1.10–3.25; p=0.005). In the current study, we provide an exhaustive description of PPFE prevalence and clinical impact in the largest cohort of SSc subjects published so far. PPFE presence should be carefully considered, due to its significant prognostic implications.
RBCs prevent rapid PIEZO1 inactivation and expose slow deactivation as a mechanism of dehydrated hereditary stomatocytosis
Authors: Elizabeth L. Evans, Oleksandr V. Povstyan, Dario De Vecchis, Fraser Macrae, Laeticia Lichtenstein, T. Simon Futers, Gregory Parsonage, Neil E. Humphreys, Antony Adamson, Antreas C. Kalli, Melanie J. Ludlow, David J. Beech
Journal: Blood (2020)
Impaired Interleukin‐27–Mediated Control of <scp>CD</scp> 4+ T Cell Function Impact on Ectopic Lymphoid Structure Formation in Patients With Sjögren's Syndrome
Authors: Davide Lucchesi, Rachel Coleby, Elena Pontarini, Edoardo Prediletto, Felice Rivellese, David G. Hill, Alicia Derrac Soria, Simon A. Jones, Ian R. Humphreys, Nurhan Sutcliffe, Anwar R. Tappuni, Costantino Pitzalis, Gareth W. Jones, Michele Bombardieri
Journal: Arthritis & Rheumatology (2020)

Ectopic lymphoid structures (ELS) develop at sites of infection, autoimmunity, and cancer. In patients with Sjögren's syndrome (SS), ELS support autoreactive B cell activation and lymphomagenesis. Interleukin-27 (IL-27) is a key regulator of adaptive immunity and limits Th17 cell-driven pathology. We undertook this study to elucidate the role of IL-27 in ELS formation and function in autoimmunity using a murine model of sialadenitis and in patients with SS.
The Nlrp3 inflammasome as a “rising star” in studies of normal and malignant hematopoiesis
Authors: Mariusz Z. Ratajczak, Kamila Bujko, Monika Cymer, Arjun Thapa, Mateusz Adamiak, Janina Ratajczak, Ahmed K. Abdel-Latif, Magda Kucia
Journal: Leukemia (2020)

Abstract Recent investigations indicate that hematopoiesis is coregulated by innate immunity signals and by pathways characteristic of the activation of innate immunity cells that also operate in normal hematopoietic stem progenitor cells (HSPCs). This should not be surprising because of the common developmental origin of these cells from a hemato/lymphopoietic stem cell. An important integrating factor is the Nlrp3 inflammasome, which has emerged as a major sensor of changes in body microenvironments, cell activation, and cell metabolic activity. It is currently the best-studied member of the inflammasome family expressed in hematopoietic and lymphopoietic cells, including also HSPCs. It is proposed as playing a role in (i) the development and expansion of HSPCs, (ii) their release from bone marrow (BM) into peripheral blood (PB) in stress situations and during pharmacological mobilization, (iii) their homing to BM after transplantation, and (iv) their aging and the regulation of hematopoietic cell metabolism. The Nlrp3 inflammasome is also involved in certain hematological pathologies, including (i) myelodysplastic syndrome, (ii) myeloproliferative neoplasms, (iii) leukemia, and (iv) graft-versus-host disease (GvHD) after transplantation. The aim of this review is to shed more light on this intriguing intracellular protein complex that has become a “rising star” in studies focused on both normal steady-state and pathological hematopoiesis.
Exercise intolerance in chronic thromboembolic pulmonary hypertension after pulmonary angioplasty
Authors: Hanako Kikuchi, Ayumi Goda, Kaori Takeuchi, Takumi Inami, Takashi Kohno, Konomi Sakata, Kyoko Soejima, Toru Satoh
Journal: European Respiratory Journal (2020)

Introduction Exercise pulmonary hypertension is common in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who experience shortness of breath during exercise and reduced exercise capacity despite normalised pulmonary arterial pressure (PAP) at rest; however, the relationship between exercise pulmonary hypertension and exercise capacity remains unclear. Here we aimed to determine whether exercise pulmonary hypertension is related to exercise capacity and ventilatory efficiency in CTEPH patients with normalised resting haemodynamics after pulmonary balloon angioplasty (BPA). Patients and methods In total, 249 patients with CTEPH treated with BPA (mean± sd age 63±14 years; male:female 62:187) with normal mean PAP (mPAP) (&lt;25 mmHg) and pulmonary arterial wedge pressure (≤15 mmHg) at rest underwent cardiopulmonary exercise testing with right heart catheterisation. mPAP–cardiac output (CO) during exercise was plotted using multipoint plots. Exercise pulmonary hypertension was defined by a mPAP–CO slope &gt;3.0. Results At rest, pulmonary vascular resistance was significantly higher in the exercise pulmonary hypertension group (n=116) than in the non-exercise pulmonary hypertension group (n=133). Lower peak oxygen consumption (13.5±3.8 versus 16.6±4.7 mL·min −1 ·kg −1 ; p&lt;0.001) was observed in the former group. The mPAP–CO slope was negatively correlated with peak oxygen consumption (r= −0.45, p&lt;0.001) and positively correlated with the minute ventilation versus carbon dioxide output slope (r=0.39, p&lt;0.001). Conclusions Impaired exercise capacity and ventilatory efficiency were observed in patients with CTEPH who had normalised PAP at rest but exercise pulmonary hypertension.
Inhibition of TGF-β-receptor signaling augments the antitumor function of ROR1-specific CAR T-cells against triple-negative breast cancer
Authors: Tanja Stüber, Razieh Monjezi, Lars Wallstabe, Johanna Kühnemundt, Sarah Louise Nietzer, Gudrun Dandekar, Achim Wöckel, Hermann Einsele, Jörg Wischhusen, Michael Hudecek
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immunotherapy with chimeric antigen receptor (CAR)-engineered T-cells is effective in some hematologic tumors. In solid tumors, however, sustained antitumor responses after CAR T-cell therapy remain to be demonstrated both in the pre-clinical and clinical setting. A perceived barrier to the efficacy of CAR T-cell therapy in solid tumors is the hostile tumor microenvironment where immunosuppressive soluble factors like transforming growth factor (TGF)-β are thought to inhibit the cellular immune response. Here, we analyzed whether CAR T-cells specific for the receptor tyrosine kinase-like orphan receptor 1 (ROR1) antigen, that is frequently expressed in triple-negative breast cancer (TNBC), are susceptible to inhibition by TGF-β and evaluated TGF-β-receptor signaling blockade as a way of neutralizing the inhibitory effect of this cytokine. Methods CD8 + and CD4 + ROR1-CAR T-cells were prepared from healthy donors and their antitumor function analyzed using the TNBC cell line MDA-MB-231 in vitro and in a microphysiologic 3D tumor model. Analyses were performed in co-culture assays of ROR1-CAR T-cells and MDA-MB-231 cells with addition of exogenous TGF-β. Results The data show that exposure to TGF-β engages TGF-β-receptor signaling in CD8 + and CD4 + ROR1-CAR T-cells as evidenced by phosphorylation of small mothers against decapentaplegic homolog 2. In the presence of TGF-β, the cytolytic activity, cytokine production and proliferation of ROR1-CAR T-cells in co-culture with MDA-MB-231 TNBC cells were markedly impaired, and the viability of ROR1-CAR T-cells reduced. Blockade of TGF-β-receptor signaling with the specific kinase inhibitor SD-208 was able to protect CD8 + and CD4 + ROR1-CAR T-cells from the inhibitory effect of TGF-β, and sustained their antitumor function in vitro and in the microphysiologic 3D tumor model. Combination treatment with SD-208 also led to increased viability and lower expression of PD-1 on ROR1-CAR T-cells at the end of the antitumor response. Conclusion We demonstrate the TGF-β suppresses the antitumor function of ROR1-CAR T-cells against TNBC in preclinical models. Our study supports the continued preclinical development and the clinical evaluation of combination treatments that shield CAR T-cells from TGF-β, as exemplified by the TGF-β-receptor kinase inhibitor SD-208 in this study.
Thrombopoietin Administration Alleviates Hematopoietic Stem Cells Intrinsic Long Term Ionizing Radiation Damages. Identification of Preferential Cellular Expansion Sites
Authors: Diana Tronik-Le Roux, Johnny Nehme, Arthur Simonnet, Pierre Vaigot, Marie Anne Nicola, Paquita Nurden, Philippe Leboulch
Journal: Blood (2008)
Pulmonary Function in Pediatric survivors of non-Malignant Disorders after Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Megan S Motosue, Hiroto Inaba, Jianmin Pan, Dennis C. Stokes, Deo Kumar Srivastava, Kimberly A. Kasow, Gregory A. Hale, Wing Leung
Journal: Blood (2008)
Multicenter randomized trial of endoscopic papillary large balloon dilation without sphincterotomy versus endoscopic sphincterotomy for removal of bile duct stones: MARVELOUS trial
Authors: Hirofumi Kogure, Shuhei Kawahata, Tsuyoshi Mukai, Shinpei Doi, Takuji Iwashita, Tesshin Ban, Yukiko Ito, Hiroshi Kawakami, Tsuyoshi Hayashi, Naoki Sasahira, Kensuke Kubota, Osamu Togawa, Hironari Kato, Yoshinobu Okabe, Saburo Matsubara, Hiroshi Yagioka, Tomotaka Saito, Yousuke Nakai, Hiroyuki Isayama
Journal: Endoscopy (2020)

Abstract Background Endoscopic papillary large balloon dilation (EPLBD) has been increasingly used for the management of large common bile duct (CBD) stones. Although EPLBD is often preceded by endoscopic sphincterotomy (EST), EPLBD alone without EST has been increasingly reported as an alternative to EST for large CBD stones. Methods This multicenter randomized trial was conducted at 19 Japanese institutions to compare the efficacy and safety of EPLBD alone versus EST for the removal of large (≥ 10 mm) CBD stones. The primary end point was complete stone removal in a single session. The secondary end points included: overall complete stone removal, lithotripsy use, procedure time, adverse events, and cost. Results 171 patients with large CBD stones were included in the analysis. The rate of single-session complete stone removal was significantly higher in the EPLBD-alone group than in the EST group (90.7 % vs. 78.8 %; P = 0.04). Lithotripsy use was significantly less frequent in the EPLBD group than in the EST group (30.2 % vs. 48.2 %; P = 0.02). The rates of early adverse events were comparable between the two groups: rates of overall adverse events were 9.3 % vs. 9.4 % and of pancreatitis were 4.7 % vs. 5.9 % in the EPLBD and EST groups, respectively. The procedure costs were $1442 vs. $1661 in the EPLBD and EST groups, respectively (P = 0.12). Conclusion EPLBD without EST for the endoscopic treatment of large CBD stones achieved a significantly higher rate of complete stone removal in a single session compared with EST, without increasing adverse events.
Targeting inducible costimulator expressed on CXCR5+PD-1+ TH cells suppresses the progression of pemphigus vulgaris
Authors: A Reum Kim, Dawoon Han, Ji Young Choi, Joon Seok, Song-Ee Kim, Seong-Hoon Seo, Hayato Takahashi, Masayuki Amagai, Su-Hyung Park, Soo-Chan Kim, Eui-Cheol Shin, Jong Hoon Kim
Journal: Journal of Allergy and Clinical Immunology (2020)