tbuckley/cabot-search huggingface dataset:
Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT
Authors: Annalisa Ruggeri, Myriam Labopin, Andrea Bacigalupo, Boris Afanasyev, Jan J. Cornelissen, Ahmet Elmaagacli, Maija Itälä-Remes, Didier Blaise, Ellen Meijer, Yener Koc, Noel Milpied, Harry C. Schouten, Nicolaus Kroeger, Mohamad Mohty, Arnon Nagler
Journal: Journal of Hematology & Oncology (2018)

Experience using post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis in allogeneic stem cell transplantation (HSCT) from matched sibling donors (MSD) or unrelated donors (UD) is limited and with controversial results. The study aim was to evaluate PT-Cy as GVHD prophylaxis post-HSCT from MSD and UD transplants. We analyzed 423 patients with acute leukemia who received PT-Cy alone or in combination with other immunosuppressive (IS) drugs as GVHD prophylaxis. Seventy-eight patients received PT-Cy alone (group 1); 204 received PT-Cy in combination with one IS drug—cyclosporine-A (CSA) or methotrexate (MTX) or mycophenolate-mofetil (MMF) (group 2), while 141 patients received PT-Cy in combination with two IS drugs—CSA + MTX or CSA + MMF (group 3). Transplants were performed from 2007 to 2015 and median follow-up was 20 months. Probability of overall survival (OS) at 2 years was 50, 52.2, and 62.4%, for the three groups, respectively, p = 0.06. In multivariate analysis, in comparison to PT-Cy alone, the addition of two IS drugs was associated with reduced risk of extensive cGVHD (HR 0.25, p = 0.02). Use of bone marrow (BM) and anti-thymocyte globulin were independently associated with reduced risk of extensive cGVHD. Prognostic factors for non-relapse mortality (NRM) were the addition of two IS drugs to PT-Cy (HR 0.35, p = 0.04), diagnosis of AML, disease status at transplant, and patient CMV serology. Factors associated with increased OS were the use of PT-Cy with two IS drugs (HR 0.49, p = 0.02), AML, and disease status at transplant. For GVHD prophylaxis in MSD and UD HSCT, the addition of IS drugs to PT-Cy enhances its effect and reduces the risk of severe cGVHD, reducing mortality and improving survival.
T Berry Brazelton: caused “Copernican revolution” in the study of child development
Authors: Ned Stafford
Journal: BMJ (2018)

As a child growing up in Waco, Texas, T Berry Brazelton possessed an uncanny ability to connect with babies. “Berry, you’re so good with babies,” his grandmother would tell him. So good was he, that at family events young Berry—still a child himself—was assigned childcare duties for his younger cousins.



“I became adept at handling many small children at once,” Brazelton wrote in his 2013 memoir, Learning to Listen: A Life Caring for Children . “I could keep them amused and safe and keep them from crying for up to two hours at a time. A miraculous feat, I realise today.”

By the age of 9, Brazelton had decided that children would be the focus of his life. “I knew I wanted to be a paediatrician,” he recalled years later. He fulfilled his childhood ambition and went on to become the pre-eminent paediatrician in the final decades of the 20th century, focusing on newborn babies as they developed to the age of 3.

His extraordinary ability to mentally connect and communicate with babies earned him the nickname “the Baby Whisperer.” He once said: “I can look at a child, a newborn, and tell you just what he is trying to say without words.”1 That ability, combined with his keen observational skills, provided Brazelton with an illuminating insight into the mind of the baby, which led to development of the neonatal behavioural assessment scale (NBAS), considered by many to be his most important contribution.2



The scale, published in 1973 and revised in the mid-1980s and again in the mid-1990s, is now used by physicians and researchers around the world to evaluate physical and neurological responses of newborn babies and their emotional wellbeing and differences. The scale helped transform paediatrics, child development, and parenting.

Barry M Lester, director of the …
Author Correction: Analysis of DNA methylation in cancer: location revisited
Authors: Alexander Koch, Sophie C. Joosten, Zheng Feng, Tim C. de Ruijter, Muriel X. Draht, Veerle Melotte, Kim M. Smits, Jurgen Veeck, James G. Herman, Leander Van Neste, Wim Van Criekinge, Tim de Meyer, Manon van Engeland
Journal: Nature Reviews Clinical Oncology (2018)
ER stress in prostate cancer: A therapeutically exploitable vulnerability?
Authors: Christopher Logothetis, Ana Aparicio, Timothy C. Thompson
Journal: Science Translational Medicine (2018)

Cooperative oncogenic effects resulting from the loss of PTEN and overexpression of MYC overcome the deleterious effects of endoplasmic reticulum stress not only to promote the growth of aggressive prostate cancer but also to expose a new therapy target for this disease (Nguyen et al ., this issue).
Participation of Women in Clinical Trials Supporting FDA Approval of Cardiovascular Drugs
Authors: Pamela E. Scott, Ellis F. Unger, Marjorie R. Jenkins, Mary Ross Southworth, Tzu-Yun McDowell, Ruth J. Geller, Merina Elahi, Robert J. Temple, Janet Woodcock
Journal: Journal of the American College of Cardiology (2018)

Concerns exist that women are underrepresented in trials of cardiovascular medications. The authors sought to examine women’s participation and the reported safety and efficacy by gender for pivotal cardiovascular disease (CVD) trials submitted to the U.S. Food and Drug Administration (FDA) supporting marketing applications. On the basis of publicly available FDA reviews, the authors assessed enrollment of women in trials supporting 36 drug approvals from 2005 to 2015. Prevalence-corrected estimates for the participation of women were calculated as the percentage of women among trial participants divided by the percentage of women in the disease population (participation to prevalence ratio [PPR]), with a range between 0.8 and 1.2 reflecting similar representation of women in the trial and disease population. Sex differences in efficacy and safety were assessed. The proportion of women enrolled ranged from 22% to 81% (mean 46%). The calculated PPR by disease area was within or above the desirable range for atrial fibrillation (0.8 to 1.1), hypertension (0.9), and pulmonary arterial hypertension (1.4); PPR was <0.8 for heart failure (0.5 to 0.6), coronary artery disease (0.6), and acute coronary syndrome/myocardial infarction (0.6). The authors found little indication of clinically meaningful gender differences in efficacy or safety. Gender differences in efficacy or safety were described in labeling for 4 drugs. Women were well represented in trials of drugs for hypertension and atrial fibrillation, and overrepresented for pulmonary arterial hypertension. Representation of women fell below a PPR of 0.8 for trials in heart failure, coronary artery disease, and acute coronary syndrome. Minimal gender differences in drug efficacy and safety profiles were observed.
P163Plasma ADAMTS13 activity in chronic thromboembolic pulmonary hypertension
Authors: A Panzenboeck, R Sadushi-Kolici, B Plaimauer, H Gritsch, P L Turecek, I Lang
Journal: Cardiovascular Research (2018)

Several physiologic substances were identified to potentiate platelet activation induced by primary agonists.Thrombopoietin (TPO) is not only a growth and development factor for the platelet precursor cell, but also can potentiate platelet response to ADP, collagen, thrombin, epinephrine, serotonin, and vasopressin.Nowadays an increasing number of patients may be chronically treated with aspirin alone or in combination with P2Y12 receptor inhibitors prior to acute coronary syndrome manifestation.Surprisingly, several studies identified aspirin pretreatment as an independent risk factor for adverse thrombotic events.Purpose: of the study was to evaluate the impact of antiplatelet pretreatment on platelet priming in patients with ST segment elevation myocardial infarction (STEMI).Materials and methods.We enrolled 40 male patients admitted to ICU due to STEMI.Levels of TPO, stromal cell derived factor 1 (SCD1) and myeloproliferative leukemia virus oncogene (MPL) were measured in plasma samples obtained at admission, on the 2nd and the 7th days since STEMI manifestation with commercially available ELISA kits.Platelet functional testing was performed at admission and on the 7th day by impedance and lumiaggregometry.Results: 33.3% of patients received antiplatelet therapy (23.3% aspirin only) before STEMI manifestation.Those patients with aspirin pretreatment were older (p ¼ 0.049), more likely to be hypertensive.There was no difference in platelet count, PCT or MPV in pretreated and non-pretreated groups.ADP induced platelet aggregation at admission was significantly suppressed by prior aspirin treatment: 0.0 (0.0 ;4.0) vs 2.0 (1.0; 7.0) Ohm, p ¼ 0.031.All patients revealed moderately to significantly elevated TPO levels at admission with no differences in those with and without pretreatment: 264.82 (153.32;337.64) vs 256.49(161.17;299.41) pg/mL, p ¼ 0.869.In aspirin naı ¨ve patients TPO dynamics was of U-shape with significant reduction on the 2nd day, compared to aspirin pretreated patients (p ¼ 0.047)."Monotonous" profiles of TPO were associated with significantly higher levels of secreted ATP in ADP stimulated platelets: 0.42 (0.2; 0.8) vs 0.16 (0.0; 0.33) nmole, p ¼ 0.03.Moderate to strong negative correlations between TPO, SCD1, MPL and collagen, but not ADP induced platelet aggregation and secretion were detected.Conclusion.Aspirin pretreatment significantly modifies thrombopoietin profiles in STEMI patients.Platelet functional heterogeneity in patients with STEMI is deepened through unequal exposure to platelet primers.
NFATc1 Promotes Antitumoral Effector Functions and Memory CD8+ T-cell Differentiation during Non–Small Cell Lung Cancer Development
Authors: Lisanne Heim, Juliane Friedrich, Marina Engelhardt, Denis I. Trufa, Carol I. Geppert, Ralf J. Rieker, Horia Sirbu, Susetta Finotto
Journal: Cancer Research (2018)

Abstract Nuclear factor of activated T cells 1 (NFATc1) is a transcription factor activated by T-cell receptor (TCR) and Ca2+ signaling that affects T-cell activation and effector function. Upon tumor antigen challenge, TCR and calcium-release–activated channels are induced, promoting NFAT dephosphorylation and translocation into the nucleus. In this study, we report a progressive decrease of NFATc1 in lung tumor tissue and in tumor-infiltrating lymphocytes (TIL) of patients suffering from advanced-stage non–small cell lung cancer (NSCLC). Mice harboring conditionally inactivated NFATc1 in T cells (NFATc1ΔCD4) showed increased lung tumor growth associated with impaired T-cell activation and function. Furthermore, in the absence of NFATc1, reduced IL2 influenced the development of memory CD8+ T cells. We found a reduction of effector memory and CD103+ tissue-resident memory (TRM) T cells in the lung of tumor-bearing NFATc1ΔCD4 mice, underlining an impaired cytotoxic T-cell response and a reduced TRM tissue-homing capacity. In CD4+ICOS+ T cells, programmed cell death 1 (PD-1) was induced in the draining lymph nodes of these mice and associated with lung tumor cell growth. Targeting PD-1 resulted in NFATc1 induction in CD4+ and CD8+ T cells in tumor-bearing mice and was associated with increased antitumor cytotoxic functions. This study reveals a role of NFATc1 in the activation and cytotoxic functions of T cells, in the development of memory CD8+ T-cell subsets, and in the regulation of T-cell exhaustion. These data underline the indispensability of NFATc1 for successful antitumor immune responses in patients with NSCLC. Significance: The multifaceted role of NFATc1 in the activation and function of T cells during lung cancer development makes it a critical participant in antitumor immune responses in patients with NSCLC. Cancer Res; 78(13); 3619–33. ©2018 AACR.
A mobile application for the management and follow-up of patients with Non-Alcoholic Fatty Liver Disease
Authors: R. Forlano, B.H. Mullish, N. Katertsidis, N. Giannakeas, A. Tzallas, M. Tsipouras, M. Yee, S. Taylor-Robinson, M. Thursz, P. Manousou
Journal: Journal of Hepatology (2018)
Electroconvulsive therapy of acute manic episodes: a review of 50 years' experience
Authors: S Mukherjee, H A Sackeim, D B Schnur
Journal: American Journal of Psychiatry (1994)

The most common indication for electroconvulsive therapy (ECT) is major depression. It is less recognized that ECT is effective also in the treatment of acute mania. This article aims to provide a comprehensive and critical review of the literature on the use of ECT for manic patients.All published papers in the English language on the use of ECT in acute mania that could be found were reviewed with regard to efficacy, frequency and number of treatments, bilateral versus unilateral electrode placement, predictors of antimanic response, stability of therapeutic response, cognitive consequences, and other relevant issues.The evidence indicates that ECT is associated with remission or marked clinical improvement in 80% of manic patients and that it is an effective treatment for patients whose manic episodes have responded poorly to pharmacotherapy. Manic patients do not require a high frequency or prolonged course of treatments to respond to ECT. The seizure threshold appears to be lower in manic patients than in depressed patients. The issues of relapse following response to ECT, cognitive consequences of ECT, and the relative merits of unilateral versus bilateral ECT in manic patients require further study.ECT is an effective and safe treatment for acute mania. Remission of mania following ECT reflects a primary therapeutic effect rather than a secondary consequence of an ECT-induced organic brain syndrome.
Eradication of hepatitis C virus in patients with decompensated cirrhosis does not improve the management of ascites after one year of follow-up
Authors: A. Juanola, I. Graupera, A. Risso, G. Mezzano, S. Lens, Z. Mariño, X. Ariza, E. Solà, V. Hernandez-Gea, X. Forns, P. Ginès
Journal: Journal of Hepatology (2018)
Immunomodulatory mechanisms of the novel therapeutic bile acid 24-nor-ursodeoxycholic acid
Authors: C.I. Zhu, N. Boucheron, C.D. Fuchs, H. Baazim, A. Lercher, E. Halilbasic, M. Tardelli, A. Bergthaler, W. Ellmeier, M. Trauner
Journal: Journal of Hepatology (2018)
Whole exome sequencing identifies rare nonsense mutations enriched among patients with advanced fibrosis due to nonalcoholic steatohepatitis
Authors: P.R. Shea, A. Sanyal, S. Harrison, V. Ratziu, R. Loomba, S. Caldwell, S. Kleinstein, B. Mccolgan, M. Subramanian, J.G. Mchutchison, R. Myers, Z. Goodman, M. Abdelmalek, J. Bosch, N. Afdhal, D. Goldstein
Journal: Journal of Hepatology (2018)
Abstract 16049: A Comparison of Short- and Medium-Term Outcomes Between Men and Women Undergoing Percutaneous Coronary Intervention in a Chinese Population During the Contemporary Era of Drug-Eluting Stents
Authors: Peiyuan He, Yuejin Yang, Shubin Qiao, Bo Xu, Yongjian Wu, Jinqing Yuan, Haibo Liu, Jun Dai, Xinran Tang, Yang Wang, Wei Li, Runlin Gao
Journal: Circulation (2014)

Background: Very few studies have compared the percutaneous coronary intervention (PCI) outcomes between men and women among Asian population in the era of drug-eluting stents (DES). We aimed to evaluate the sex-specific disparities in a Chinese population. Methods: From June 1, 2006 to April 30, 2011, a total of 21,964 coronary artery disease patients who have undergone PCI with stents implantation were included from one single Chinese heart center. Among them, 17209 were males, and 4755 were females. The primary endpoint was defined as major cardiovascular events (MACE) during hospitalization and at 1 year follow-up, which included cardiac death, myocardial infarction (MI), and target vessel revascularization (TVR). The secondary endpoint was defined as each component of MACE. Major bleeding after the procedure was recognized as the safety endpoint. Results: The rates of MACE during hospitalization and at 1 year follow-up were similar between men and women (in-hospital: 1.5% vs. 1.6%, P=0.730, at 1 year follow-up: 4.0% vs. 4.1%, P=0.589). The adjusted rates of the primary endpoint was still similar (in-hospital odds ratio [OR], 0.94; 95% confidence interval [CI], 0.66–1.33, at 1 year follow-up hazard ratio [HR], 1.00; 95% CI, 0.96-1.04). No significant differences were detected in each component of MACE (P all &gt; 0.05). But major bleeding after PCI occurred more in women than in men (1.2% vs. 0.7%, P=0.002), mainly driven by the access site-related major bleeding (0.8% vs. 0.4%, P=0.002). The access site complications were also more frequent in women (2.5% vs. 1.6%, P &lt;0.001). Conclusions: In the Chinese population with frequent use of DES, women present similar in-hospital and 1 year major outcomes compared with men. But women have higher risk of major bleeding and access site complications.
Semaphorin 4D correlates with increased bone resorption, hypercalcemia, and disease stage in newly diagnosed patients with multiple myeloma
Authors: Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Dimitrios Christoulas, Tina Bagratuni, Marios Bakogeorgos, Maria Gavriatopoulou, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Efstathios Kastritis, Meletios A. Dimopoulos
Journal: Blood Cancer Journal (2018)

Multiple myeloma (MM) is characterized by bone destruction due to increased bone resorption and decreased bone formation. Semaphorin 4D (CD100, Sema4D) is expressed by osteoclasts, binds to its receptor Plexin-B1, and acts as a mediator of osteoclast-osteoblast interaction that ultimately inhibits osteoblastic bone formation. Preclinical data suggest that Sema4D/Plexin-B1 pathway is implicated in MM-induced bone disease. However, there is no information on the role of Sema4D in MM patients. Thus, we evaluated Sema4D and Plexin-B1 in six myeloma cells lines in vitro; in the bone marrow plasma (BMP) and serum of 72 newly diagnosed symptomatic MM (NDMM) patients and in 25 healthy controls. Only one myeloma cell line produced high Sema4D. BMP and circulating Sema4D and Plexin-B1 levels were significantly higher in MM patients compared to controls (p < 0.01). Sema4D correlated with serum calcium levels (p < 0.001), increased bone resorption (as assessed by CTX; p < 0.01), and ISS (p < 0.001). There was a trend for higher Sema4D levels in patients with osteolysis (p = 0.07), while patients with diffuse MRI pattern had higher BMP Sema4D levels (p = 0.02). Our data suggest that Sema4D is elevated in MM patients and correlate with adverse myeloma features and increased bone resorption, providing a possible target for novel therapeutic approaches in MM.
Pediatric Patient With Cerebral Metastasis From Papillary Thyroid Cancer
Authors: Katrina Korhonen, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2018)

Abstract Brain metastasis from papillary thyroid carcinoma is uncommon. Concurrent cerebral and pulmonary metastases from papillary thyroid carcinoma is rare, especially in pediatric patients. We report a case of a brain metastasis revealed on post-therapy 131 I scan in a 12 year old girl with thyroid cancer who also had diffuse pulmonary metastases which were partially responsive to sequential 131 I therapy.
Presence of steatosis does not increase the risk of Hepatocellular Carcinoma in patients with Chronic Hepatitis B over long follow-up
Authors: C.T. Lim, B.B.G. Goh, K.H.T. Lim, W.Q. Leow, R. Azhar, W.K. Wan, R. Kumar
Journal: Journal of Hepatology (2018)
Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications
Authors: Bryant R England, Geoffrey M Thiele, Daniel R Anderson, Ted R Mikuls
Journal: BMJ (2018)

<h3>ABSTRACT</h3> Rheumatoid arthritis is a systemic autoimmune disease characterized by excess morbidity and mortality from cardiovascular disease. Mechanisms linking rheumatoid arthritis and cardiovascular disease include shared inflammatory mediators, post-translational modifications of peptides/proteins and subsequent immune responses, alterations in the composition and function of lipoproteins, increased oxidative stress, and endothelial dysfunction. Despite a growing understanding of these mechanisms and their complex interplay with conventional cardiovascular risk factors, optimal approaches of risk stratification, prevention, and treatment in the context of rheumatoid arthritis remain unknown. A multifaceted approach to reduce the burden posed by cardiovascular disease requires optimal management of traditional risk factors in addition to those intrinsic to rheumatoid arthritis such as increased disease activity. Treatments for rheumatoid arthritis seem to exert differential effects on cardiovascular risk as well as the mechanisms linking these conditions. More research is needed to establish whether preferential rheumatoid arthritis therapies exist in terms of prevention of cardiovascular disease. Ultimately, understanding the unique mechanisms for cardiovascular disease in rheumatoid arthritis will aid in risk stratification and the identification of novel targets for meaningful reduction of cardiovascular risk in this patient population.
Lipidome Evolution in Mammalian Tissues
Authors: Ekaterina Khrameeva, Ilia Kurochkin, Katarzyna Bozek, Patrick Giavalisco, Philipp Khaitovich
Journal: Molecular Biology and Evolution (2018)

Lipids are essential structural and functional components of cells. Little is known, however, about the evolution of lipid composition in different tissues. Here, we report a large-scale analysis of the lipidome evolution in six tissues of 32 species representing primates, rodents, and bats. While changes in genes' sequence and expression accumulate proportionally to the phylogenetic distances, <2% of the lipidome evolves this way. Yet, lipids constituting this 2% cluster in specific functions shared among all tissues. Among species, human show the largest amount of species-specific lipidome differences. Many of the uniquely human lipidome features localize in the brain cortex and cluster in specific pathways implicated in cognitive disorders.
Low‐Dose Interleukin‐2 for Refractory Autoimmune Hepatitis
Authors: Tiong Y. Lim, Marc Martinez‐Llordella, Elisavet Kodela, Elisabeth Gray, Michael A. Heneghan, Alberto Sanchez‐Fueyo
Journal: Hepatology (2018)

Lim, Tiong Y.; Martinez‐Llordella, Marc; Kodela, Elisavet; Gray, Elisabeth; Heneghan, Michael A.; Sanchez‐Fueyo, Alberto , M.D., Ph.D. Author Information
The ProC3 marker of type III collagen formation accurately reflects hepatic inflammation and fibrosis stage in asymptomatic alcoholic liver disease patients
Authors: M. Thiele, M.J. Nielsen, B.S. Madsen, M. Kjærgaard, J. Hansen, S. Antonsen, L.M. Rasmussen, D. Leeming, S. Detlefsen, M. Karsdal, A. Krag
Journal: Journal of Hepatology (2018)
Sorafenib/Regorafenib resistance and BH3-mimetics efficacy in hepatocellular carcinoma treatment is determined by mitochondrial changes in the BCL-2 profile
Authors: A. Tutusaus, M. Stefanovic, B. Cucarull, M. Mari, L. Boix, M. Reig, J. Bruix, A. Morales
Journal: Journal of Hepatology (2018)