tbuckley/cabot-search huggingface dataset:
Role of Eros, a novel transmembrane protein, in regulation of host defence
Authors: David C Thomas, Simon Clare, John M Sowerby, Mercedes Pardo, Jatinder K Juss, David A Goulding, Louise Van der Weyden, Daniel M L Storisteanu, Ananth Prakash, Marion Espeli, Shaun Flint, James C Lee, Kim Hoenderdos, Leanne Kane, Katherine Harcourt, Subhankar Mukhopadhyay, Yagnesh Umrania, Robin Antrobus, David Adams, Alex Bateman, Jyoti S Choudhary, Paul A Lyons, Alison M Condliffe, Edwin R Chilvers, Gordon Dougan, Kenneth G C Smith
Journal: The Lancet (2016)
Guidelines help doctors to identify sepsis earlier
Authors: Susan Mayor
Journal: BMJ (2016)

A fast respiratory rate, altered mental status, and low blood pressure are the three key symptoms that doctors can use to identify sepsis and start treatment earlier, a new global consensus1 has recommended. The consensus redefines sepsis and septic shock with the aims of making them easier to diagnose and of reducing associated deaths.

A panel of 19 sepsis specialists from around the world reviewed the available literature, epidemiological data, and expert opinion on how to differentiate sepsis from …
Molecular evolution of the human immunodeficiency and related viruses.
Authors: S Yokoyama, L Chung, T Gojobori
Journal: Molecular Biology and Evolution (1988)

A phylogenetic tree for different human immunodeficiency viruses type 1 (HIV1) and type 2 (HIV2), lentiviruses, and oncoviruses has been constructed by comparing the nucleotide sequences of the two regions of their pol genes that encode the reverse transcriptase and endonuclease/integrase. The analysis indicates that (1) different HIV1 strains form one cluster and their common ancestor diverged from the ancestor of HIV2, (2) the common ancestor of the HIV1 and HIV2 strains diverged from that of the lentivirus, and (3) the common ancestor of the lentivirus group and that of the oncoviruses diverged earlier than that. Divergence between the HIV1 and HIV2 strains seems to have occurred greater than 200 years ago, implying that AIDS has existed for a long time but went undetected. Furthermore, nonsynonymous changes are occurring uniformly through time, whereas synonymous changes are more variable among different lineages.
Immunotherapy for neuro-oncology: the critical rationale for combinatorial therapy
Authors: David A. Reardon, Mark R. Gilbert, Wolfgang Wick, Linda Liau
Journal: Neuro-Oncology (2015)

A successful therapeutic paradigm established historically in oncology involves combining agents with potentially complementary mechanisms of antitumor activity into rationally designed regimens. For example, cocktails of cytotoxic agents, which were carefully designed based on mechanisms of action, dose, and scheduling considerations, have led to dramatic improvements in survival including cures for childhood leukemia, Hodgkin's lymphoma, and several other complex cancers. Outcome for glioblastoma, the most common primary malignant CNS cancer, has been more modest, but nonetheless our current standard of care derives from confirmation that combination therapy surpasses single modality therapy. Immunotherapy has recently come of age for medical oncology with exciting therapeutic benefits achieved by several types of agents including vaccines, adoptive T cells, and immune checkpoint inhibitors against several types of cancers. Nonetheless, most benefits are relatively short, while others are durable but are limited to a minority of treated patients. Critical factors limiting efficacy of immunotherapeutics include insufficient immunogenicity and/or inadequate ability to overcome immunosuppressive factors exploited by tumors. The paradigm of rationally designed combinatorial regimens, originally established by cytotoxic therapy for oncology, may also prove relevant for immunotherapy. Realization of the true therapeutic potential of immunotherapy for medical oncology and neuro-oncology patients may require development of combinatorial regimens that optimize immunogenicity and target tumor adaptive immunosuppressive factors.
Further distinctions between manic-depressive illness (bipolar disorder) and primary depressive disorder (unipolar depression)
Authors: G Winokur, W Coryell, J Endicott, H Akiskal
Journal: American Journal of Psychiatry (1993)

Patients with bipolar disorder differ from patients with unipolar depression by having family histories of mania with an earlier onset and by having more episodes over a lifetime. This study was designed to determine whether additional aspects of course of illness, the presence of medical diseases, childhood traits, and other familial illnesses separate the two groups.In a large collaborative study, consecutively admitted bipolar and unipolar patients were systematically given clinical interviews. Data were collected on medical diseases and childhood behavioral traits. Systematic family history and family study data were also obtained. The patients were studied every 6 months for 5 years.The group of bipolar patients had an earlier onset, a more acute onset, more total episodes, and more familial mania and were more likely to be male. These differences were relatively independent of each other. The bipolar patients were also more likely to have shown traits of hyperactivity as children. The unipolar patients had a significantly greater number of lifetime medical/surgical interventions than the bipolar patients, even when age was controlled. Alcoholism was more frequently found in the families of the bipolar patients, even when alcoholism in the probands was controlled; however, this difference was not significant.This study supports the usefulness of distinguishing between bipolar and unipolar patients in treatment and research studies.
K1 from human herpesvirus 8 (HHV-8) suppresses Fas-mediated apoptosis and binds to the Fas complex
Authors: F. Samaniego, S. Wang, D. Young, S. Wang
Journal: Journal of Clinical Oncology (2005)

6585 Background: HHV-8 is associated with the development of primary effusion lymphoma (PEL) and Kaposi’s sarcoma. PEL-derived cell lines express the HHV-8 K1 gene spontaneously. K1 codes for a transmembrane protein, containing a short cytosolic tail, with an immunoreceptor tyrosine-based activation motif (ITAM). ITAMs are present in receptors regulating cell activation and survival. K1 in transgenic mice, driven by a constitutive promoter, is associated with development of lymph node hyperplasia and lymphoma. Given its NF-κB activation inducing properties, we anticipate that K1 contributes to transformation, in part, by suppression of apoptosis. Methods: To study the role of HHV8 K1 gene product, we generated K1 stably expressing cell line BJABK1 and vector alone cell line BJABXS, with retrovirus vector pLXSN, and packaging cell line PT67 NIH 3T3. We also expressed a truncated K1 lacking the ITAM (K1m). Anti-Fas antibody (CH-11) was used to induce apoptosis and cells were monitored for membrane protein Annexin-V, DNA integrity, and morphological features of apoptosis. C-FLIP, caspase 8 and Fas were monitored by immunoblot analysis and flow cytometry. K1 was expressed in mouse hepatocytes by intravenous inoculation of plasmids, expressing K1 and green fluorescent protein. K1-Fas complex interactions were analyzed. Results: K1 is expressed in PEL cells and primary cells. Anti-Fas antibody induced apoptosis was suppressed in BJABK1 cells compared with BJABK1m and BJABXS cells. K1 expression suppressed apoptosis, which had been induced by Fas ligand. K1 expression did not suppress apoptosis induced by TRAIL or radiation. K1 expressing cells showed consistent lower levels of procaspase 8 cleavage products. Immunoprecipitation-immunoblot analysis with anti-Fas and anti-myc antibodies indicated Fas and K1myc were bound to the same complex. Conclusions: Taken together, the data indicate that expression of HHV8 K1 can suppress Fas-mediated apoptosis. K1 and Fas bind to the same complex in several cell types and in vivo. We anticipate K1 regulates apoptosis through binding of the Fas complex and represents a novel form of apoptosis regulation. No significant financial relationships to disclose.
Update: Interim Guidelines for Health Care Providers Caring for Infants and Children with Possible Zika Virus Infection — United States, February 2016
Authors: Katherine E. Fleming-Dutra, Jennifer M. Nelson, Marc Fischer, J. Erin Staples, Mateusz P. Karwowski, Paul Mead, Julie Villanueva, Christina M. Renquist, Anna A. Minta, Denise J. Jamieson, Margaret A. Honein, Cynthia A. Moore, Sonja A. Rasmussen
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

CDC has updated its interim guidelines for U.S. health care providers caring for infants born to mothers who traveled to or resided in areas with Zika virus transmission during pregnancy and expanded guidelines to include infants and children with possible acute Zika virus disease. This update contains a new recommendation for routine care for infants born to mothers who traveled to or resided in areas with Zika virus transmission during pregnancy but did not receive Zika virus testing, when the infant has a normal head circumference, normal prenatal and postnatal ultrasounds (if performed), and normal physical examination. Acute Zika virus disease should be suspected in an infant or child aged <18 years who 1) traveled to or resided in an affected area within the past 2 weeks and 2) has ≥2 of the following manifestations: fever, rash, conjunctivitis, or arthralgia. Because maternal-infant transmission of Zika virus during delivery is possible, acute Zika virus disease should also be suspected in an infant during the first 2 weeks of life 1) whose mother traveled to or resided in an affected area within 2 weeks of delivery and 2) who has ≥2 of the following manifestations: fever, rash, conjunctivitis, or arthralgia. Evidence suggests that Zika virus illness in children is usually mild. As an arboviral disease, Zika virus disease is nationally notifiable. Health care providers should report suspected cases of Zika virus disease to their local, state, or territorial health departments to arrange testing and so that action can be taken to reduce the risk for local Zika virus transmission. As new information becomes available, these guidelines will be updated: http://www.cdc.gov/zika/.
Prospective study of specialist oncology community nursing resulting in improvements in key patient supportive care outcomes
Authors: J. Sussman, D. Howell, T. Whelan, K. Brazil, N. Pyette, D. Bainbridge
Journal: Journal of Clinical Oncology (2007)

9107 Background: Cancer patients report ongoing significant gaps in supportive care. To date few interventions have been shown to improve supportive care outcomes in cancer. Research in other areas suggests that specialist nursing interventions in the community may address gaps in unmet need, continuity of care and quality of life. This study prospectively studied a community based nursing intervention for cancer patients. Methods: Patients were followed using a longitudinal cohort design, with assessments at baseline (T1), four (T2) and eight (T3) weeks, upon enrollment in a specialist nursing program. The nursing intervention included a comprehensive supportive care assessment and subsequent care delivery or linkage to appropriate services in the community. Validated patient assessment outcomes included: Supportive Cancer Needs Survey Short Form 34, Quality of Life (EORTC QLC-30 (v3) ), Continuity and Coordination of Care (CCCQ), and a service utilization instrument. Results: 72 of 109 enrolled patients completed all study measures. The majority had advanced stage disease. Median age was 59 years. Disease categories for participants included: breast (33%), gastrointestinal. (18.1%), lung (13.9%), ovarian (9.7%), and head and neck (8.3%). All participants received a baseline comprehensive assessment and had a mean of 1.7 home visits with a mean of 3.9 telephone contacts. We observed significant reductions in most supportive care need domains ( Table ). There were trends to improvement in domains of quality of life and continuity of care. We also observed reductions in acute care services use and increased community agency use. Conclusions: This is one of the first prospective studies in cancer patients that demonstrates improvements in a number of supportive care outcomes through a community based specialist nursing intervention. A randomized study to confirm these findings is currently underway. [Table: see text] No significant financial relationships to disclose.
Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma
Authors: Y. Shi, M. Dong, X. Hong, W. Zhang, J. Feng, J. Zhu, L. Yu, X. Ke, H. Huang, Z. Shen, Y. Fan, W. Li, X. Zhao, J. Qi, H. Huang, D. Zhou, Z. Ning, X. Lu
Journal: Annals of Oncology (2015)
Comparison of 2 doses of daunorubicin(45mg/m<sup>2</sup> vs 60mg/m<sup>2</sup>) in induction therapy of patients of de novo acute myeloid leukemia
Authors: N. Khattry, L. Kumar, R. Kumar, C. Patel, V. Raina, A. Sharma, P. Chandra, M. Bhutani, M. Sengar, V. Kochupillai
Journal: Journal of Clinical Oncology (2006)

6581 Background: Standard induction regimen for the management of acute myeloid leukemia (AML) includes 45 mg/m 2 of daunorubicin (DNR) × 3 days and 100 mg/m 2 of ara-c × 7 days. Recent studies suggest that higher doses of DNR may have better outcome. Randomized studies to objectively authenticate these observations to the best of our knowledge are not available. This study was undertaken as a preliminary trial to compare the induction remission rates and toxicity of 60 mg/m 2 of DNR with standard dose of 45 mg/m 2 . Methods: Sixty newly diagnosed AML patients, except AML—M3, from January 2003—May 2005 were randomized to either 45mg/m 2 (group A ) or 60 mg/m 2 (group B) of DNR for three days. The dose of ara-c was 100mg/m 2 for 7 days in both groups. All denovo AML patients with 0–2 performance status (ECOG) were included in the study. Results: Fifty six patients were evaluable, 30 in group A and 26 in group B. The baseline demographic and clinical characteristics were comparable. Twenty (67%) patients in group A and 23 (88%) in group B (p=0.05) achieved complete remission (CR). Fifteen (50%) patients in group A and 22 (84.6%) in group B (p=0.006) achieved remission after single course of induction chemotherapy. Nine patients (30%) in group A and 3 (11.5%) in group B died due to uncontrolled sepsis (p=0.09). Five patients, all belonging to Group A, had persistent disease at the time of death. Though there was no significant difference with respect to major organ toxicities in both the groups, duration of grade 4 thrombocytopenia and duration of admission were significantly greater in group A (P=0.02 and P=0.005 respectively). Conclusions: This study indicates that daunorubicin in the dose of 60 mg/m 2 is superior to 45mg/m 2 as a remission induction therapy for AML patients with good performance status. Further follow up is required to ascertain whether higher remission rate leads to higher disease free and over all survival. No significant financial relationships to disclose.
Zoledronic acid (ZA) effectively inhibits cancer treatment-induced bone loss (CTIBL) in postmenopausal women (PMW) with early breast cancer (BCa) receiving adjuvant letrozole (Let): 12 mos BMD results of the Z-FAST trial
Authors: A. Brufsky, W. G. Harker, J. T. Beck, R. Carroll, E. Tan-Chiu, C. Seidler, L. Lacerna, E. Thomas, E. Perez
Journal: Journal of Clinical Oncology (2005)

533 Background: Aromatase inhibitors (AIs) are effective therapies for PMW with BCa. Their use has been associated with increased bone resorption markers and bone loss at the lumbar spine (LS)/total hip (TH). This multicenter open-label randomized study evaluates the efficacy and safety of ZA in preventing CTIBL in PMW with early BCa who are receiving AI therapy. Methods: 602 PMW with stage I-IIIa ER+ and/or PR+ BCa starting Let (2.5 mg qd x 5 yrs) were randomized to upfront ZA (4 mg IV infusion q 6 mos) vs delayed ZA in 93 centers in the US and Canada. The delayed group will receive ZA when either post-baseline T-score decreases <−2 SD or in case of fracture. The primary endpoint is the percent change in LS BMD at 12 mos. Results: Baseline characteristics were similar between groups. 343 of 602 pts (170 upfront/173 delayed) are evaluable for 12 mos LS BMD. Upfront ZA group shows a mean increase of 2.02% while the delayed group shows a mean decrease of 2.61%, resulting in a significant difference of 4.63% between groups (p<0.001). 347 of 602 pts (175 upfront/172 delayed) are evaluable for 12 mos TH BMD. Upfront ZA group shows a mean increase of 1.40% while the delayed group shows a mean decrease of 2.10%, resulting in a significant difference of 3.50% between groups (p<0.001). Serum markers of bone turnover (N-Telopeptide, Bone-Specific Alkaline Phosphatase) were collected and analyzed on a subset of 226 pts at 3 month intervals for 1 yr. The results showed significant suppression of both markers over 12 mos in favor of upfront vs delayed ZA group. ZA was safe and well tolerated. Updated 12 mos BMD data on all pts will be presented at the meeting. Conclusions: Upfront ZA prevents CTIBL in PMW with early BCa receiving adjuvant Let at 12 mos. ZA in combination with Let in this setting offers the potential to combine the anti-cancer efficacy of Let with the bone protective effect of ZA. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Couple screening would be easier for many centres
Authors: R. A Doherty, L. A Bradley, J. E Haddow
Journal: BMJ (1996)

EDITOR,—H S Cuckle and colleagues provide further economic evidence supporting antenatal screening for cystic fibrosis.1 The couple model is estimated to cost more than the sequential model, largely because of retesting in subsequent pregnancies if the woman's partner has changed. However, the estimate takes into account neither the cost nor the complexity of counselling and other contact with the patients in the sequential model. The cost of counselling would be modest, but locating each woman who was a carrier, explaining the need for and obtaining …
Abstract 16029: Twenty-Year Outcome After the Ross Operation in Neonates, Infants and Children: Results From the Italian Pediatric Ross Registry
Authors: Giovanni Battista Luciani, Gianluca Lucchese, Adriano Carotti, Gianluca Brancaccio, Piero Abbruzzese, Giuseppe Caianiello, Lorenzo Galletti, Gaetano Gargiulo, Stefano Marianeschi, Alessandro Mazzucco, Bruno Murzi, Carlo Pace Napoleone, Marco Pozzi, Lucio Zannini, Alessandro Frigiola
Journal: Circulation (2013)

Objective: To define current outcome after Ross operation in children a nation-wide multi-center study covering 22 years of experience was undertaken. Methods: Between 1990-2013, 305 (178 male) pat...
Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis
Authors: Michael A. Gimbrone, Guillermo García-Cardeña
Journal: Circulation Research (2016)

Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease. Endothelial cell dysfunction, in its broadest sense, encompasses a constellation of various nonadaptive alterations in functional phenotype, which have important implications for the regulation of hemostasis and thrombosis, local vascular tone and redox balance, and the orchestration of acute and chronic inflammatory reactions within the arterial wall. In this review, we trace the evolution of the concept of endothelial cell dysfunction, focusing on recent insights into the cellular and molecular mechanisms that underlie its pivotal roles in atherosclerotic lesion initiation and progression; explore its relationship to classic, as well as more recently defined, clinical risk factors for atherosclerotic cardiovascular disease; consider current approaches to the clinical assessment of endothelial cell dysfunction; and outline some promising new directions for its early detection and treatment.
Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older
Authors: Takaaki Konuma, Nobuhiro Tsukada, Junya Kanda, Naoyuki Uchida, Yuju Ohno, Shigesaburo Miyakoshi, Heiwa Kanamori, Michihiro Hidaka, Toru Sakura, Makoto Onizuka, Naoki Kobayashi, Masashi Sawa, Tetsuya Eto, Yoshiko Matsuhashi, Koji Kato, Tatsuo Ichinohe, Yoshiko Atsuta, Koichi Miyamura
Journal: American Journal of Hematology (2016)

Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT.
Disregulated Osteogenesis By Mesenchymal Stromal Cells (MSC) After In Vivo Exposure To Multiple Myeloma: Studies In a Novel Humanized Mouse Model For Bone Remodelling In Myeloma
Authors: Richard W.J. Groen, Willy A. Noort, Jessica Sigmans, Aniek van Stralen, Linda Aalders, Reinier Raymakers, Huipin Yuan, Constantine S. Mitsiades, Anton Martens
Journal: Blood (2013)
Evaluating Chemotherapy at the End of Life
Authors: Norbert Frickhofen, Bernd Oliver Maier
Journal: JAMA Oncology (2016)

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A prospective double-blinded randomized controlled trial comparing systemic stress response in Laparoascopic cholecystectomy between low-pressure and standard-pressure pneumoperitoneum
Authors: Saeed Shoar, Mohammad Naderan, Hossein Ebrahimpour, Ahmadreza Soroush, Shirzad Nasiri, Ali Movafegh, Zhamak Khorgami
Journal: International Journal of Surgery (2016)