tbuckley/cabot-search huggingface dataset:
Serotonergic and noradrenergic dysregulation in alcoholism: m- chlorophenylpiperazine and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects
Authors: J H Krystal, E Webb, N L Cooney, H R Kranzler, S W Southwick, G R Heninger, D S Charney
Journal: American Journal of Psychiatry (1996)

This study compared serotonergic (5-HT) and noradrenergic reactivity in recently detoxified alcoholic patients and healthy comparison subjects.Participants were 22 male inpatients who met DSM-III-R criteria for alcohol dependence and who were abstinent for 12-26 days and 13 male healthy comparison subjects. Subjects completed 3 days of testing over 2 weeks under double-blind conditions that involved the intravenous infusions of m-chlorophenylpiperazine (mCPP), yohimbine, or a saline placebo. Drug effects on mood, physiologic responses, and plasma levels of cortisol, prolactin, and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured.Both mCPP and yohimbine infusion increased nervousness, vital signs, and plasma cortisol, prolactin, and MHPG levels relative to placebo Cortisol responses to mCPP were blunted in the alcoholic patients relative to the comparison subjects. Cortisol and prolactin responses to yohimbine were greater in the alcoholic patients, whereas their pulse increases after yohimbine infusion were blunted. No group differences emerged in MHPG, nervousness, or blood pressure responses to either drug.This study documents persistent alterations in neuroendocrine responsivity of both 5-HT and noradrenergic systems in alcoholic patients after detoxification. Blunted cortisol responses to mCPP in these recently detoxified patients may reflect reductions in 5-HT2 receptor function. The absence of altered MHPG responses to yohimbine in the alcoholic patients suggests that presynaptic noradrenergic responsivity is not persistently altered in these patients. In contrast, the enhanced cortisol responses and reduced pulse responses to yohimbine in alcoholic patients may reflect down-regulation of postsynaptic noradrenergic receptors.
Multi-host transmission dynamics of Schistosoma japonicum: the China perspective (Comment)
Authors: Darren Gray
Journal: PLoS Medicine (2008)

Author: Donald P. McManus Position: Professor and Laboratory Head Institution: Molecular Prasitology Laboratory, The Queensland Institute of Medical Research, Brisbane, Australia E-mail: donM@qimr.edu.au Additional Authors: Darren J. Gray, Gail M. Williams, Yuesheng Li Submitted Date: February 28, 2008 Published Date: February 28, 2008 This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.
急性呼吸道感染时建议“大量饮水”的证据：系统性综述
Authors: 赵长安, 王槿芳
Journal: BMJ (2004)

医生们常常建议呼吸道感染的患者多喝水。这个忠告从理论上说有利于弥补因发热和呼吸道蒸发所致的非显性失水的增多，纠正摄入减少引起的失水，降低呼吸道分泌液的粘度。在很多人看来，如此忠告的合理性不证自明，因为即使其益处不确定或充其量益处不大，但是至少没有害处。
Dasatinib (BMS-354825), a Multi-Targeted Kinase Inhibitor, Inhibits the Kinase Activity of Wild-Type, Juxtamembrane and Activation Loop Mutant Kit Isoforms Associated with Human Malignancies.
Authors: Marcus M. Schittenhelm, Sharon Shiraga, Arin Schroeder, Amie S. Corbin, Diana Griffith, Francis Y. Lee, Michael W. Deininger, Brian J. Druker, Michael C. Heinrich
Journal: Blood (2005)
The Role of Lipoprotein (a) as a Marker of Residual Risk in Patients With Diabetes and Established Cardiovascular Disease on Optimal Medical Therapy: Post Hoc Analysis of ACCELERATE
Authors: Nishant P. Shah, Qiuqing Wang, Katherine E. Wolski, Leslie Cho, Ellen McErlean, Giacomo Ruotolo, Govinda Weerakkody, Jeffrey S. Riesmeyer, Stephen J. Nicholls, A. Michael Lincoff, Steven E. Nissen, Venu Menon
Journal: Diabetes Care (2019)

Despite optimal medical treatment, patients with diabetes and established atherosclerotic disease remain at high risk for recurrent cardiovascular events. Consequently, identification and modification of novel risk factors that mediate residual risk remain an important clinical priority. Lipoprotein (a) [Lp(a)] is an LDL-like particle in which apolipoprotein B is covalently bound by a single disulfide bond to apolipoprotein A, and it has both thrombotic and proinflammatory characteristics (1). There is also a growing body of evidence showing causality of atherosclerotic disease with elevated Lp(a) (1). However, little is known about the predictive role of Lp(a) in patients with diabetes and established cardiovascular disease receiving optimal medical treatment. Thus, given that Lp(a) is an established marker of cardiovascular disease with targeted therapies currently in clinical trials (NCT03070782, ClinicalTrials.gov), we sought to see the impact of elevated Lp(a) in a high-risk secondary prevention cohort of patients with diabetes on optimal medical treatment enrolled in the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes (ACCELERATE) trial to identify patients who could potentially benefit from Lp(a)-targeted treatment (2).

In our post hoc analysis, participants who met eligibility to enroll in the trial were divided into patients with and without diabetes to assess the impact of Lp(a) tertiles in each group. Baseline Lp(a) levels (in nmol/L) were measured by a central laboratory, using the …
A Novel Sphingomyelin Synthase Gene, SMS1-Regulated Sphingomyelin/Ceramide-Rich Microdomain Plays a Crucial Role in Fas-Mediated Apoptosis.
Authors: Michihiko Miyaji, Shohei Yamaoka, Jin Zhe Xiong, Ryuichi Amakawa, Tsuneyo Mimori, Shirou Fukuhara, Hisanori Umehara, Toshiro Okazaki
Journal: Blood (2004)
Serum Ferritin in Children with Sickle Cell Disease on Chronic Transfusion: Measure of Iron Overload or End Organ Injury? STOP/STOP II Liver Iron Ancillary Study.
Authors: Tom Adamkiewicz, Miguel R. Abboud, Julio C. Barredo, Melanie Kirby-Allen, Ofelia A. Alvarez, James F. Casella, Rathi V. Iyer, Virgil McKie, Gerald Milton Woods, Abdullah Kutlar, Carole Paley, Jessica Peterson, Elizabeth Rackoff, Manuela Merelles-Pulcini, Elizabeth Dackiw, Kristin Stegenga, Nadine Odo, Mimi Lou, Robert J. Adams
Journal: Blood (2006)
Molecular Identity of <i>I</i> <sub>to</sub>
Authors: David McKinnon
Journal: Circulation Research (1999)

ur understanding of the function of the Kv1.4 K ϩ channel in cardiac physiology has changed over time.The Kv1.4 gene was the first mammalian gene identified that encoded a rapidly inactivating or transient K ϩ channel. 1,2Previous attempts at cloning mammalian K ϩ channels based on homology to the Drosophila Shaker gene, which encodes a rapidly inactivating channel, had unexpectedly turned up several delayed rectifier channels.There were high expectations, therefore, when the Kv1.4 gene was shown to encode a transient channel, and it was quite reasonably suggested that the Kv1.4 channel could underlie the transient outward K ϩ current (I to ) in cardiac muscle. 2 A rival for the affections of I to aficionados soon appeared, however, with the identification of a second family of transient channels, which contained two members known as Kv4.1 and Kv4.2. 3,4On the basis of the observation that the Kv4.2 gene was expressed in heart, it was suggested that these channels also might underlie the I to . 5nitial interest in the molecular basis of the I to focused almost exclusively on Kv1.4, 6 -8however, and the Kv4.2 channel languished largely unnoticed.There were several reasons for this.The Kv4.2 channel, when expressed in Xenopus oocytes, was something of an ugly duckling.It activated more slowly than I to , and its inactivation phase was complex and incomplete, with multiple inactivation rates and a noninactivating sustained component. 4This unfavorable aesthetic appearance was largely due to the limitations of the Xenopus oocyte expression system used in the initial studies, which appears to lack a factor that can modify the kinetic properties of the channel. 9The molecular identity of this factor remains a mystery, but it is apparently ubiquitous, because the Kv4.2 channel, when expressed in most mammalian cell lines, has fast kinetics, more closely resembling the kinetic properties of I to . 10The sensitivity of the Kv4.2 channel to blockade by 4-aminopyridine (4-AP) was lower than expected, 5 although this also appears to be due at least in part to the oocyte expression system, with generally higher sensitivity found when the channel is expressed in cell lines. 10
Does general anesthesia affect neurodevelopment in infants and children?
Authors: Mary Ellen McCann, Sulpicio G Soriano
Journal: BMJ (2019)

Abstract General anesthesia has been unequivocally linked to abnormal development of the central nervous system, leading to neurocognitive impairments in laboratory models. In vitro and in vivo studies have consistently shown that exposure to GABA agonists (eg, volatile anesthetics, midazolam, and propofol) or NMDA antagonists (eg, ketamine, isoflurane, and nitrous oxide) produces dose dependent and developmental age dependent effects on various neuronal transmission systems. Exposure to these drugs increases neuronal cell death in juvenile animals including rats, mice, and non-human primates. The possibility of anesthetic induced neurotoxicity occurring in children has led to concerns about the safety of pediatric anesthesia. A spectrum of behavioral changes has been documented after general anesthetic exposure in young children, including emergence delirium, which may be evidence of toxicity. Most clinical studies are retrospective; specifics about medications or monitoring are unavailable and many of the outcomes may not be sensitive to detect small neurocognitive deficits. Some of these retrospective studies have shown an association between anesthesia exposure at a young age and neurocognitive deficits, but others have not. Practitioners and families should be reassured that although general anesthetics have the potential to induce neurotoxicity, very little clinical evidence exists to support this.
Analysis of Metformin Effects on Bone Marrow Fibrosis and Disease Progression in Primary Myelofibrosis Patients: Preliminary Results of an Open Label Phase II Trial (FIBROMET)
Authors: Paula De Melo Campos, Katia B Pagnano, Rubia Mancuso, Francisco Breno S. Teófilo, Juan L Coelho-Silva, Fernanda I Della Via, Leandro Luiz Lopes Freitas, Hernandes F. Carvalho, Fernando Ferreira Costa, Fabiola Traina, Sara T Olalla Saad
Journal: Blood (2019)
KLHDC8B Is a Novel, Mitotically-Regulated Classical Hodgkin’s Lymphoma Candidate Susceptibility Gene.
Authors: Mathew E. Mealiffe, Tomas Kirchhoff, Peter H. Wiernik, Henry T. Lynch, Masanori Daibata, Anne-Marie Gerdes, Kenneth Offit, Lynn R. Goldin, Marshall S. Horwitz
Journal: Blood (2006)
Optimizing Chimeric Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia
Authors: Noelle V. Frey, Pamela A. Shaw, Elizabeth O. Hexner, Edward Pequignot, Saar Gill, Selina M. Luger, James K. Mangan, Alison W. Loren, Alexander E. Perl, Shannon L. Maude, Stephan A. Grupp, Nirav N. Shah, Joan Gilmore, Simon F. Lacey, Jos J. Melenhorst, Bruce L. Levine, Carl H. June, David L. Porter
Journal: Journal of Clinical Oncology (2019)

The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel (CTL019) has an 81% response rate in children with relapsed or chemotherapy refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). Cytokine release syndrome (CRS) is a life-threatening treatment-related toxicity that limits the full therapeutic potential in adults. We report outcomes for adults with r/r ALL treated with an optimized CTL019 dosing and CRS management strategy.
Circulating tumor cells (CTCs) and epithelial mesenchymal transition (EMT) in primary breast cancer.
Authors: Marian Karaba, Michal Mego, Gabriel Minarik, Juraj Benca, Tatiana Sedlackova, Denisa Manasova, Gabriela Sieberova, Zuzana Hlavata, Andrej Jurik, Tomas Minarik, Jan Macuch, Paulina Gronesova, Eva Oravcova, Veronika Svabova, Jozef Sufliarsky, Juraj Pechan, James M. Reuben, Jozef Mardiak
Journal: Journal of Clinical Oncology (2013)

e22023 Background: CTCs are prognostic in breast cancer (BC) patients and represent a heterogeneous population of cells with different phenotypes and biological value. EMT gives rise to cells with stem cell-like properties with increased chemotherapy resistance and may be responsible for under detection of CTCs by currently approved assays. The aim of this study was to characterize CTCs based on the expression of epithelial and mesenchymal markers in non-metastatic BC patients. Methods: This prospective ongoing study included 124 patients (pts) with non-metastatic BC enrolled from March 2012 to December 2012. CTCs were detected before surgery (124 pts), before 1 st cycle (28 pts) and before 2 nd cycle (23 pts) of adjuvant therapy. Isolated peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep kit negative selection with anti-CD45 antibody. RNA extracted from CD45-depleted (CD45 - ) PBMC was interrogated for expression of EMT-inducing transcription factors (TWIST1, SNAIL1, SLUG, ZEB1) and epithelial (CK19) gene transcripts by qRT-PCR. Expressions of gene transcripts in CD45 - PBMC of patients were compared to those of CD45 - PBMC of 60 healthy donors. Results: CTCs were detected in 26.6% pts before surgery, in 21.4% pts before 1 st cycle and in 43.5% of pts before 2 nd cycle of adjuvant therapy. Before surgery, CTCs exhibiting only epithelial makers were present in 12.9% pts, whereas CTCs with only EMT markers were observed in 12.1% of pts and CTCs coepressing both markers were detected in 1.6% pts. There was a trend for higher CTC positivity in high grade, triple negative tumors and in the presence of lymphovascular invasion. We detected CTCs with only an EMT phenotype more often in pts with N+ than in N0 disease (20.4% vs. 10.2%; p = 0.03) and in pts after 1 st cycle of adjuvant chemotherapy compared to before surgery (30.4% vs. 12.1%; p = 0.03). There was no association between epithelial CTCs and analyzed clinico-pathological variables. Conclusions: Our data suggest that CTCs with EMT phenotype are involved in tumor dissemination and treatment resistance, and support the role of EMT in cancer pathogenesis. Moreover, these results underlay the concept of CTCs heterogeneity.
Generation of a new xenogenic transplantation model for the analysis of undifferentiated pleomorphic sarcoma: NOS in mice.
Authors: Thomas Wehler, Marc Becker, Nadine Grebe, Matthias Theobald, Pol Maria Rommens, Dirk Proschek, Claudine Graf
Journal: Journal of Clinical Oncology (2013)

e21505 Background: Undifferentiated pleomorphic sarcoma, NOS (not otherwise specified) formerly known as MFH comprise about 15-20% of all soft tissue sarcomas (STS) in adults. This kind of sarcoma is characterized by low response to radiation or chemotherapy. Thus, surgery with the aim of R0-resection is still the cornerstone for a curative treatment regimen. However, surgery is not always possible. In the recent past, many efforts have been undertaken to refine chemotherapeutic options and to develop new drugs for targeted therapies, such as mTOR-inhibtors or tyrosine kinase inhibitors. Yet, the hoped break through is still lacking. In addition, the further development of entity-based new drugs is difficult due to the low incidence of STS and suitable reproducible animal models. Here, we present a new xenogenic transplantation model of a pleomorphic sarcoma in mice. Methods: After intraoperative resection of the sarcoma, a sarcoma-derived cell line was established. These cultured cells were injected s.c. (1x10E6 cells) in immunocompromised NOD/SCID γc-/- mice and in humanized NOD/SCID γc-/- mice. Results: Tumor growth was reproducibly seen after four to six weeks. When resected after 12 weeks, the xenogenic tumor presented the same histological and morphological characteristics as the original tumor. Tumor infiltrating lymphocytes were detected by immunhistochemical staining. Conclusions: This new xenogenic transplantation model can serve as a basis for the evaluation of manifold questions within the fields of oncology, tumor genetics and tumor immunology.
The Occurrence of Cytomegalovirus Gastrointestinal Disease in Patients with Gastrointestinal Graft-Versus-Host Disease and Its Related Clinical Outcomes in the Era of Preemptive Therapy for Cytomegalovirus Infection
Authors: Byung-Sik Cho, Seung-Ah Yahng, Jae-Ho Yoon, Seung-Hwan Shin, Sung-Eun Lee, Ki-Seong Eom, Yoo-Jin Kim, Heeje Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Chong-Won Park
Journal: Blood (2011)
The Disease-Risk Stratification Scheme (DRSS), a Contemporary Risk-Stratification System for Allogeneic Stem Cell Transplantation
Authors: Roni Shouval, Joshua A Fein, Myriam Labopin, Ali Bazarbachi, Frédéric Baron, Gesine Bug, Fabio Ciceri, Selim Corbacioglu, Sebastian Giebel, Maria H Gilleece, Silvia Montoto, Zinaida Peric, Emmanuelle Polge, Annalisa Ruggeri, Jaime Sanz, Bipin N. Savani, Christoph Schmid, Alexandros Spyridonidis, Jurjen Versluis, Ibrahim Yakoub-Agha, Mohamad Mohty, Arnon Nagler
Journal: Blood (2019)
Malignant Gliomas: Simplifying the Complexity
Authors: Howard A. Fine
Journal: Cancer Discovery (2019)

Abstract Summary: The dramatic intertumoral and intratumoral heterogeneity in glioblastoma represents a formidable obstacle to finding effective combination targeted therapy for each individual patient. The article by Wang and colleagues in this issue of Cancer Discovery adds to a growing body of literature that points to these diverse aberrant genomes coalescing onto a very limited number of cellular states, reviving the hope of eventually identifying and therapeutically targeting just a few central gene-regulatory targets in most gliomas. See related article by Wang et al., p. 1708.
Dashing: fast and accurate genomic distances with HyperLogLog
Authors: Daniel N. Baker, Ben Langmead
Journal: Genome biology (2019)

Abstract Dashing is a fast and accurate software tool for estimating similarities of genomes or sequencing datasets. It uses the HyperLogLog sketch together with cardinality estimation methods that are specialized for set unions and intersections. Dashing summarizes genomes more rapidly than previous MinHash-based methods while providing greater accuracy across a wide range of input sizes and sketch sizes. It can sketch and calculate pairwise distances for over 87K genomes in 6 minutes. Dashing is open source and available at https://github.com/dnbaker/dashing .
Outcomes of Adults with Acute Lymphoblastic Leukemia (ALL) Following Relapse After First Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Authors: Amir Hamdi, LM Poon, Rima M. Saliba, Gabriela Rondon, Celina Ledesma, Muzaffar Qazilbash, Chitra M. Hosing, Roy B. Jones, Uday R. Popat, Nieto Nieto, Amin M. Alousi, Stefan O. Ciurea, Elizabeth J. Shpall, Richard E. Champlin, Partow Kebriaei
Journal: Blood (2012)
Efficacy and Tolerability of Tremelimumab in Locally Advanced or Metastatic Urothelial Carcinoma Patients Who Have Failed First-Line Platinum-Based Chemotherapy
Authors: Padmanee Sharma, Joohyuk Sohn, Sang Joon Shin, Do-Youn Oh, Bhumsuk Keam, Hyo Jin Lee, Marco Gizzi, Ewa Kalinka, Filip Y.F.L. de Vos, Dario Ruscica, Salvatore Ferro, Feng Xiao, Paul Baverel, Cecil Chi-Keung Chen, Kobby Asubonteng, Nassim Morsli, Luc Dirix
Journal: Clinical Cancer Research (2019)

Patients with advanced urothelial carcinoma who fail platinum-containing chemotherapy (treatment fails) have a poor prognosis and limited treatment options. Recent approvals of immune-checkpoint inhibitors confirmed the value of immunomodulatory therapy in urothelial carcinoma. Tremelimumab is a selective human immunoglobulin G2 (IgG2) monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 with demonstrated durable response rate in metastatic melanoma. This is the first study to report the efficacy and safety of tremelimumab in urothelial carcinoma.We report the results of the urothelial carcinoma cohort from a phase II, open-label, multicenter study of patients with advanced solid tumors (NCT02527434). Patients with locally advanced/metastatic urothelial carcinoma were treated with tremelimumab monotherapy (750 mg via intravenous infusion every 4 weeks for seven cycles, then every 12 weeks for two additional cycles) for up to 12 months or until disease progression, initiation of other anticancer therapy, unacceptable toxicity, or consent withdrawal.In 32 evaluable patients with metastatic urothelial carcinoma, objective response rate was 18.8% (95% confidence interval, 7.2-36.4), including complete response (CR) in 2 (6.3%), and partial response in 4 patients (12.5%). Median duration of response has not been reached. Stable disease of ≥12 months was reported in 1 patient (3.1%), yielding a disease control rate at 12 months of 21.9%. Overall, tremelimumab was generally well tolerated; safety results were consistent with the known safety profile.Tremelimumab monotherapy demonstrated clinical activity and durable responses in patients with metastatic urothelial carcinoma. This study is the first in which CR has been observed with tremelimumab as a single agent in urothelial carcinoma.
Gene Expression Profiles for Molecular Classification of Multiple Myeloma in Newly Diagnosed Patients Included in a Prospective, Multicenter, Phase 3 Trial.
Authors: A. Broyl, J. Peeters, D. Hose, Y. de Knegt, B. Beverloo, H. Lokhorst, H. Goldschmidt, M. van Duin, P. Sonneveld
Journal: Blood (2008)
A Novel Role of Cyclic Nucleotide Phosphodiesterase 10A in Pathological Cardiac Remodeling and Dysfunction
Authors: Si Chen, Yishuai Zhang, Janet K. Lighthouse, Deanne M. Mickelsen, Jiangbin Wu, Peng Yao, Eric M. Small, Chen Yan
Journal: Circulation (2019)

Background: Heart failure is a leading cause of death worldwide. Cyclic nucleotide phosphodiesterases (PDEs), through degradation of cyclic nucleotides, play critical roles in cardiovascular biology and disease. Our preliminary screening studies have revealed PDE10A upregulation in the diseased heart. However, the roles of PDE10A in cardiovascular biology and disease are largely uncharacterized. The current study is aimed to investigate the regulation and function of PDE10A in cardiac cells and in the progression of cardiac remodeling and dysfunction. Methods: We used isolated adult mouse cardiac myocytes and fibroblasts, as well as preclinical mouse models of hypertrophy and heart failure. The PDE10A selective inhibitor TP-10, and global PDE10A knock out mice were used. Results: We found that PDE10A expression remains relatively low in normal and exercised heart tissues. However, PDE10A is significantly upregulated in mouse and human failing hearts. In vitro, PDE10A deficiency or inhibiting PDE10A with selective inhibitor TP-10, attenuated cardiac myocyte pathological hypertrophy induced by Angiotensin II, phenylephrine, and isoproterenol, but did not affect cardiac myocyte physiological hypertrophy induced by IGF-1 (insulin-like growth factor 1). TP-10 also reduced TGF-β (transforming growth factor-β)–stimulated cardiac fibroblast activation, proliferation, migration and extracellular matrix synthesis. TP-10 treatment elevated both cAMP and cGMP levels in cardiac myocytes and cardiac fibroblasts, consistent with PDE10A as a cAMP/cGMP dual-specific PDE. In vivo, global PDE10A deficiency significantly attenuated myocardial hypertrophy, cardiac fibrosis, and dysfunction induced by chronic pressure overload via transverse aorta constriction or chronic neurohormonal stimulation via Angiotensin II infusion. Importantly, we demonstrated that the pharmacological effect of TP-10 is specifically through PDE10A inhibition. In addition, TP-10 is able to reverse pre-established cardiac hypertrophy and dysfunction. RNA-Sequencing and bioinformatics analysis further identified a PDE10A-regualted transcriptome involved in cardiac hypertrophy, fibrosis, and cardiomyopathy. Conclusions: Taken together, our study elucidates a novel role for PDE10A in the regulation of pathological cardiac remodeling and development of heart failure. Given that PDE10A has been proven to be a safe drug target, PDE10A inhibition may represent a novel therapeutic strategy for preventing and treating cardiac diseases associated with cardiac remodeling.