tbuckley/cabot-search huggingface dataset:
A comparison of Selective Aortic Arch Perfusion and Resuscitative Endovascular Balloon Occlusion of the Aorta for the management of hemorrhage-induced traumatic cardiac arrest: A translational model in large swine
Authors: Ed B. G. Barnard, James E. Manning, Jason E. Smith, Jason M. Rall, Jennifer M. Cox, James D. Ross
Journal: PLoS Medicine (2017)

Background Survival rates remain low after hemorrhage-induced traumatic cardiac arrest (TCA). Noncompressible torso hemorrhage (NCTH) is a major cause of potentially survivable trauma death. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) at the thoracic aorta (Zone 1) can limit subdiaphragmatic blood loss and allow for IV fluid resuscitation when intrinsic cardiac activity is still present. Selective Aortic Arch Perfusion (SAAP) combines thoracic aortic balloon hemorrhage control with intra-aortic oxygenated perfusion to achieve return of spontaneous circulation (ROSC) when cardiac arrest has occurred. Methods and findings Male Yorkshire Landrace cross swine (80.0 ± 6.0 kg) underwent anesthesia, instrumentation for monitoring, and splenectomy. TCA was induced by laparoscopic liver lobe resection combined with arterial catheter blood withdrawal to achieve a sustained systolic blood pressure <10 mmHg, cardiac arrest. After 3 min of arrest, swine were allocated to one of three interventions: (1) REBOA plus 4 units of IV fresh whole blood (FWB), (2) SAAP with oxygenated lactated Ringer's (LR), 1,600 mL/2 min, or (3) SAAP with oxygenated FWB 1,600 mL/2 min. Primary endpoint was survival to the end of 60 min of resuscitation, a simulated prehospital phase. Thirty animals were allocated to 3 groups (10 per group)—5 protocol exclusions resulted in a total of 35 animals being used. Baseline measurements and time to cardiac arrest were not different amongst groups. ROSC was achieved in 0/10 (0%, 95% CI 0.00–30.9) REBOA, 6/10 (60%, 95% CI 26.2–87.8) SAAP-LR and 10/10 (100%, 95% CI 69.2–100.0) SAAP-FWB animals, p < 0.001. Survival to end of simulated 60-minute prehospital resuscitation was 0/10 (0%, 95% CI 0.00–30.9) for REBOA, 1/10 (10%, 95% CI 0.25–44.5) for SAAP-LR and 9/10 (90%, 95% CI 55.5–99.7) for SAAP-FWB, p < 0.001. Total FWB infusion volume was similar for REBOA (2,452 ± 0 mL) and SAAP-FWB (2,250 ± 594 mL). This study was undertaken in laboratory conditions, and as such may have practical limitations when applied clinically. Cardiac arrest in this study was defined by intra-aortic pressure monitoring that is not feasible in clinical practice, and as such limits the generalizability of findings. Clinical trials are needed to determine if the beneficial effects of SAAP-FWB observed in this laboratory study will translate into improved survival in clinical practice. Conclusions SAAP conferred a superior short-term survival over REBOA in this large animal model of hemorrhage-induced traumatic cardiac arrest with NCTH. SAAP using an oxygen-carrying perfusate was more effective in this study than non-oxygen carrying solutions in TCA. SAAP can effect ROSC from hemorrhage-induced electrocardiographic asystole in large swine.
The relationship between parkinsonism and tardive dyskinesia
Authors: J Gerlach
Journal: American Journal of Psychiatry (1977)

The author analyzes parkinsonism and hyperkinesia in psychiatric patients with tardive dyskinesia before and during treatment with alpha-methyl-p-tyrosine (AMPT, a dopamine antagonist), biperiden (an acetylcholine antagonist), and baclofen (a GABA agonist); and in patients with paralysis agitans and L-dopa-induced hyperkinesia. AMPT and baclofen had similar influences on oral dyskinesia, resulting in reduced frequency, unchanged or slightly reduced amplitude, and increased duration of each movement. The author concludes that: 1) reduced dopaminergic activity may be the primary pathogenetic background for tardive dyskinesia; 2) dopaminergic hypersensitivity and/or cholinergic hypofunction is necessary before hyperkinesia breaks through; and 3) the neurotoxic effects of neuroleptics may be associated with age-dependent changes in nigrostriatal regions representing oral innervation.
THE EFFECT OF FUNCTIONAL FATIGUE ON KNEE FORCE SENSE IN UNINJURED ADULT MALE FOOTBALL PLAYERS
Authors: Nicholas Clark, Mark Rolleston
Journal: British Journal of Sports Medicine (2017)

Background Intact proprioception (joint position sense (JPS), kinaesthesia, force sense (FS)) is critical for optimal neuromuscular control of knee functional joint stability. Fatigue is known to impair knee JPS and kinaesthesia, but research regarding the effect of fatigue on knee FS is lacking. Objective To determine the effect of functional fatigue on knee extension FS in uninjured, adult, male football players. It was hypothesized that functional fatigue would result in significant impairment of FS. Design Single-session, pre-/post-intervention repeated measures. Setting University sensorimotor control and biomechanics laboratory. Participants University team players (n=21; age (mean±SD) 21.0±1.2 years; height 178.7±7.2 cm; mass 76.8±11.5 kg; training×2/week; match×1/week) without history of knee intra-articular derangement or surgery. Interventions Functional fatigue was defined/induced using the previously published Functional Agility Short-Term Fatigue Protocol (FAST-FP). The FAST-FP incorporated acceleration-deceleration tasks typical of football training/match play. Main Outcome Measures Dominant leg (preferred kicking leg) knee extension FS was measured in Newtons (N). Players were seated on an isokinetic dynamometer set to isometric mode, the knee flexed 45°. A knee extension target trial-reproduction trial sequence was repeated five times, the difference between trials designated the absolute error (AE), the average AE used for data analyses. Reliability and measurement error for this procedure has been previously established. Force sense measurements were performed before and immediately after the FAST-FP. The FS and FAST-FP procedures were adjacent in the same laboratory space with minimal transition time between tasks. Results Force sense AE significantly increased following fatigue (pre-fatigue=10.9±5.8 N; post-fatigue=23.0±9.2 N; difference=12.1±7.9 N; P=0.00; d=1.59). Conclusions Dominant leg knee extension FS was significantly impaired following functional fatigue. Fatigue-induced impairment of FS could result in sub-optimal neuromuscular control and altered knee functional joint stability that affects knee injury risk.
Influence of Estradiol Benzoate on Epidermal Methylcholanthrene Garcinogenesis&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: F. X. Paletta, Paul F. Max
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Influence of Estradiol Benzoate on Epidermal Methylcholanthrene Garcinogenesis Get access F. X. Paletta, F. X. Paletta research fellow Barnard Free Skin and Cancer Hospital, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul F. Max Paul F. Max assistant in gynecology Barnard Free Skin and Cancer Hospital, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 6, June 1942, Pages 577–581, https://doi.org/10.1093/jnci/2.6.577 Published: 01 June 1942
Thrombin promotes diet-induced obesity through fibrin-driven inflammation
Authors: Anna K. Kopec, Sara R. Abrahams, Sherry Thornton, Joseph S. Palumbo, Eric S. Mullins, Senad Divanovic, Hartmut Weiler, A. Phillip Owens, Nigel Mackman, Ashley Goss, Joanne van Ryn, James P. Luyendyk, Matthew J. Flick
Journal: Journal of Clinical Investigation (2017)

Obesity promotes a chronic inflammatory and hypercoagulable state that drives cardiovascular disease, type 2 diabetes, fatty liver disease, and several cancers. Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet (HFD) as well as obese patients. Fibγ390–396A mice carrying a mutant form of fibrinogen incapable of binding leukocyte αMβ2-integrin were protected from HFD-induced weight gain and elevated adiposity. Fibγ390–396A mice had markedly diminished systemic, adipose, and hepatic inflammation with reduced macrophage counts within white adipose tissue, as well as near-complete protection from development of fatty liver disease and glucose dysmetabolism. Homozygous thrombomodulin-mutant ThbdPro mice, which have elevated thrombin procoagulant function, gained more weight and developed exacerbated fatty liver disease when fed a HFD compared with WT mice. In contrast, treatment with dabigatran, a direct thrombin inhibitor, limited HFD-induced obesity development and suppressed progression of sequelae in mice with established obesity. Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese patients.
Anemia is an important prognostic factor for very elderly patients with diffuse large B-cell lymphoma treated with rituximab and attenuated chemotherapy.
Authors: Sheng-Hsuan Chien, Cheng-Hwai Tzeng, Tzeon-Jye Chiou, Po-Min Chen, Chueh-Chuan Yen, Liang-Tsai Hsiao
Journal: Journal of Clinical Oncology (2015)

e20518 Background: The combination of rituximab and attenuated chemotherapy is increasingly used to treat very elderly (age ≥ 80 years) diffuse large B-cell lymphoma (DLBCL) patients. However, prognostic factors in this patient population have not been thoroughly studied. Methods: Data were collected from 109 very elderly DLBCL patients, including clinical characteristics, treatments, toxicities, responses, and outcomes. Prognostic factors associated with overall survival (OS) and event free survival (EFS) were also analyzed. Results: The median age was 83 years, and 29% of patients were aged > 85 years. At diagnosis, 71% of patients had an age-adjusted International Prognostic Index score ≥ 2, and 60% had anemia (hemogloblin < 12 g/dL). The median doses of anthracycline and cyclophosphamide in the first cycle were reduced to 50% and 80% of reference doses, respectively. 63% of patients experienced grade 3–4 hematological toxicities and infection complications. Median OS was 10.8 months, with a 2-year OS rate of 28.4%. A multivariate analysis identified hypoalbuminemia (hazard ratio [HR] 2.78; 95% confidence interval [CI], 1.37–5.63; P = 0.004), anemia (HR 1.94; 95% CI, 1.01–3.70; P = 0.044), and marrow involvement (HR 6.84; 95% CI, 3.48–13.46; P < 0.001) as significant and independent predictors of poor OS. Regarding to grade 3-4 toxicity event as induction chemotherapy, only anemia (HR 1.76; 95% CI, 1.10–2.80; P = 0.017) was associated with EFS Conclusions: For very elderly DLBCL patients treated with rituximab and attenuated chemotherapy, anemia at diagnosis was independently associated with a poor OS and EFS.
Abstract 278: Cardiac Med1 is Necessary for Postnatal Survival in Mice
Authors: Kathryn M Spitler, Jessica M Ponce, Duane D Hall, Chad E Grueter
Journal: Circulation Research (2015)

Alterations in gene transcription are commonly associated with cardiovascular disease pathogenesis characterized by cardiomyocyte hypertrophy. The phenotypic responses result in diminished cardiac contractility, ventricular dilation, fibrosis and ultimately sudden death. The mediator complex is a crucial facilitator of gene transcription; however, few studies have investigated the role of mediator in cardiovascular disease initiation and progression. A key subunit of the Mediator complex, MED1, interacts with nuclear receptors to target gene-specific transcription. To determine the role of MED1 in regulating cardiac function, we generated a heart specific knockout of MED1 (cMED1KO). Postnatal deletion of MED1 in mice results in lethality between 3 to 6 weeks of age. The cMED1KO mice display a marked increase in heart mass compared to floxed controls. Furthermore, echocardiography and histological analysis of hearts taken at 3 weeks showed that the cMED1KO animals had decreased cardiac function, increased fibrosis and a dilated left ventricle. Transcriptional changes were observed for key markers of cardiac disease including MYH7, ANF, ACTIN1. We performed RNAseq analysis to identify changes in the transciptome between cMED1KO and floxed control hearts. The analysis unveiled changes in expression of genes regulating cardiac development, metabolism and function. Taken together these results reveal a critical role for MED1 in postnatal cardiac growth and development due to altered gene expression in adult cardiomyocytes.
Inactivation of Receptor Tyrosine Kinases Reverts Aberrant DNA Methylation in Acute Myeloid Leukemia
Authors: Na Shen, Fei Yan, Jiuxia Pang, Na Zhao, Naseema Gangat, Laichu Wu, Ann M. Bode, Aref Al-Kali, Mark R. Litzow, Shujun Liu
Journal: Clinical Cancer Research (2017)

Purpose: Receptor tyrosine kinases (RTKs) are frequently deregulated in leukemia, yet the biological consequences of this deregulation remain elusive. The mechanisms underlying aberrant methylation, a hallmark of leukemia, are not fully understood. Here we investigated the role of RTKs in methylation abnormalities and characterized the hypomethylating activities of RTK inhibitors.Experimental Design: Whether and how RTKs regulate expression of DNA methyltransferases (DNMTs), tumor suppressor genes (TSGs) as well as global and gene-specific DNA methylation were examined. The pharmacologic activities and mechanisms of actions of RTK inhibitors in vitro, ex vivo, in mice, and in nilotinib-treated leukemia patients were determined.Results: Upregulation of RTKs paralleled DNMT overexpression in leukemia cell lines and patient blasts. Knockdown of RTKs disrupted, whereas enforced expression increased DNMT expression and DNA methylation. Treatment with the RTK inhibitor, nilotinib, resulted in a reduction of Sp1-dependent DNMT1 expression, the diminution of global DNA methylation, and the upregulation of the p15INK4B gene through promoter hypomethylation in AML cell lines and patient blasts. This led to disruption of AML cell clonogenicity and promotion of cellular apoptosis without obvious changes in cell cycle. Importantly, nilotinib administration in mice and human patients with AML impaired expression of DNMTs followed by DNA hypomethylation, TSG re-expression, and leukemia regression.Conclusions: Our findings demonstrate RTKs as novel regulators of DNMT-dependent DNA methylation and define DNA methylation status in AML cells as a pharmacodynamic marker for their response to RTK-based therapy, providing new therapeutic avenues for RTK inhibitors in overcoming epigenetic abnormalities in leukemia. Clin Cancer Res; 23(20); 6254-66. ©2017 AACR.
Neurocognitive function testing and health related quality of life in stage IV lung cancer patients with and without brain metastases.
Authors: Grainne M. O'Kane, Brandon C Tse, Vivian Tam, M Catherine Brown, Lin Lu, Michael Borean, Tiffany Tse, Catherine Labbe, Hiten Naik, Nicole Mittman, Emily Tam, Mark Doherty, Natasha B. Leighl, Penelope Ann Bradbury, Frances A. Shepherd, Doris Howell, Geoffrey Liu
Journal: Journal of Clinical Oncology (2017)

2073 Background: Survival in stage IV lung cancer (S4LC) patients (pts) continues to improve, highlighting the importance of assessing health related quality of life (HRQoL). Lung cancer, involvement with brain metastases (BM), and systemic or brain-specific treatment can all impact neurocognitive function (NCF) and HRQoL. We evaluated the relationship between NCF and HRQoL in S4LC pts by BM status. Methods: S4LC pts with BM (BM+) were frequency distributionally-matched to pts without BM (NBM). NCF was measured using the Hopkins Verbal Learning Test – Revised (HVLT-R), the Controlled Oral Word Association Test (COWAT) and Trail Making Tests (TMT-A/B); scores were correlated with health utility score (HUS) data from EQ5D-3L surveys (Pearson Coefficient, R). Results: BM+ (n = 54) and matched NBM (n = 40) pts had similar demographics. The overall median age was 61years; 59% were female; of 89% that were adenocarcinomas, half had EGFR/ALK alterations; mean time since diagnosis was 2.6 years; mean time since BM were diagnosed in BM+ pts was 0.5 years. Mean HUS (mHUS) were similar between groups: 0.77 for BM+ vs. 0.78 for NBM; p = 0.86. However, pts with stable BM had higher HUS than those with progressive BM (mHUS: 0.80 vs 0.69; p = 0.045). Of BM+ pts, 44% had received whole brain radiation (WBRT). Correlations of NCF and HUS specific for BM+ pts were observed for several HLVT scores, including Total Recall (TR), which was correlated with HUS in BM+ (R = 0.35, p = 0.01) but not in NBM (R = 0.04, p = 0.84) and Recognition Discrimination Index (BM+: R = 0.32, p = 0.03 vs NBM: R = 0.13, p = 0.51). In contrast, TMT-A/B NCF test results had slightly stronger associations with HUS in NBM pts. COWAT was least associated with HUS in BM+ or NBM pts. In BM+ pts treated vs untreated with WBRT, HLVT scores were better in untreated patients (TR, p &lt; 0.0001; delayed recall, p = 0.006; retention, p = 0.089), associations not seen with either TMT-A/B or COWAT. Mutation status had no bearing on these associations. Conclusions: NCF impacts HUS in S4LC pts and should be considered in treatment planning. HVLT scores are useful to assess specifically the impact of BM and WBRT in S4LC pts, and is reflected in associations with HRQoL.
NADPH oxidase-2 derived superoxide drives mitochondrial transfer from bone marrow stromal cells to leukemic blasts
Authors: Christopher R. Marlein, Lyubov Zaitseva, Rachel E. Piddock, Stephen D. Robinson, Dylan R. Edwards, Manar S. Shafat, Zhigang Zhou, Matthew Lawes, Kristian M. Bowles, Stuart A. Rushworth
Journal: Blood (2017)
<i>Helicobacter</i> species are potent drivers of colonic T cell responses in homeostasis and inflammation
Authors: Jiani N. Chai, Yangqing Peng, Sunaina Rengarajan, Benjamin D. Solomon, Teresa L. Ai, Zeli Shen, Justin S. A. Perry, Kathryn A. Knoop, Takeshi Tanoue, Seiko Narushima, Kenya Honda, Charles O. Elson, Rodney D. Newberry, Thaddeus S. Stappenbeck, Andrew L. Kau, Daniel A. Peterson, James G. Fox, Chyi-Song Hsieh
Journal: Science Immunology (2017)

Helicobacter in the intestine induce regulatory T cells during homeostasis and effector T cells during colonic inflammation.
Efficacy of front-line chemotherapy for recurrent/metastatic adenosarcoma of the uterus.
Authors: Michael Nathenson, Anthony Paul Conley, Ravin Ratan, Maria Alejandra Zarzour, Neeta Somaiah, Dejka M. Araujo, Shreyaskumar Patel, Robert S. Benjamin, Vinod Ravi
Journal: Journal of Clinical Oncology (2016)

11058 Background: Uterine adenosarcoma is the rarest uterine sarcoma, with an age-adjusted incidence of 0.2 per 100,000 in the US population. Standard treatment involves surgical resection with hysterectomy and BSO, resulting in a 50-70% 5-yr overall survival (OS). Data regarding the responsiveness of this rare sarcoma subtype to standard sarcoma chemotherapy is lacking. The objective of this study was to review the MD Anderson experience in the treatment of this rare sarcoma specifically focusing on response to cytotoxic chemotherapy. Methods: Patients with uterine adenosarcoma seen in consultation between 1977 and 2014 were identified from the MDACC tumor registry. Clinical data was collected retrospectively. We used the Kaplan-Meier method to estimate OS and progression free survival (PFS). Response was determined using RECIST 1.1 criteria. Results: 157 Adenosarcoma Pts, with a mean age of 52 yrs, were identified. 60 developed local recurrence, 5 developed metastatic disease, and 10 developed both. Median OS for those Pts that developed locally recurrent and/or metastatic disease was 5.5 yrs. 58 of these Pts received at least one line of chemotherapy and constituted the study population. OS and PFS from 1st line chemotherapy for those Pts was16 mo and 7.6 mo, respectively. Response rate (complete + partial response) and stable disease per RECIST for 1st line chemotherapy were 40.0% (4/10) and 50% (5/10) for doxorubicin (dox) based regimens and 25% (2/8) and 37.5% (3/8) for gemcitabine/docetaxel (G/D). Median PFS for 1st line chemotherapy dox based regimens was 5.4 mo, for G/D was 15.7 mo. Median OS for 1stline chemotherapy dox based regimens was 12.9 mo, for G/D 24.9 mo. Potential confounders in this study, leading to these discordant results, are treatment with concurrent surgery or hormonal therapies. Conclusions: Adenosarcomas possess both epithelial and mesenchymal components and seem to respond less to G/D compared to dox based regimens. However, PFS is higher with G/D. If goal of therapy is to produce reduction in size of the tumor prior to surgery, dox based chemotherapy may have advantages. In the treatment of metastatic or unresectable disease where preservation of quality of life is needed, G/D may be the optimal choice.
The effect of radiation therapy (RT) on overall survival in surgically resected gastric cancer (GC): A population based analysis.
Authors: Henry Vuong, Gurinder Singh Sidhu
Journal: Journal of Clinical Oncology (2015)

e15015 Background: GC is surgically curable and the role of adjuvant chemotherapy (CT) and RT is evolving. The current standard is adjuvant CT and RT with 5FU. Perioperative CT without RT was more recently shown to be successful. The benefit of RT to overall survival (OS) is unclear. Methods: We reviewed data from the Surveillance, Epidemiology and End Results (SEER) data registry for patients with GC. The data was analyzed using Microsoft Excel and SPSS statistical software. The SEER registry does not provide data about CT. Results: We analyzed 44,022 patients diagnosed with GC between 2004 – 10 with AJCC6 staging. The median age at diagnosis was 70 years old, of which 60.6% were men, 39.4 % were women, 71% were White, and 14% were Black. Of these, 13.1%, 8.7%, 9.5%, 7.9%, 1.8%, 35.2% were Stage IA, IB, II, IIIA, IIIB, and IV respectively, with the rest unknown. Of the patients who underwent surgery, the median OS of patients who did and did not undergo RT was 32.5 vs. 39 months in Stage IA (p<0.01), 33 vs. 30 months in Stage IB (p=0.45), 29 vs. 19 months in Stage II (p<0.01), 22 vs. 13 months in Stage IIIA (p<0.01), and 20 vs. 12 months in Stage IIIB (p<0.01). Stage IV was diagnosed in 15,472 patients; 3,703 underwent surgical resection and 1,015 underwent RT. Median OS of patients who did and did not undergo surgery was 10 vs. 3 months (p<0.01). Median OS of patients who did and did not undergo RT was 14 vs. 12 months (p<0.01). Patients with Grade 1 and 2 tumors had better OS compared to those with grade 3 and 4 tumors in Stage IB, II, and IIIA disease while no significant difference was seen in Stage I A and IIIB disease (Table). Conclusions: Patients with GC who undergo surgery benefit from RT in Stage II, IIIA, and IIIB; but not in Stage IA and IB disease. Patients with low grade tumors survive longer than patients with high grade tumors. Patients with Stage IV GC also benefitted from RT and/or surgery. While this analysis is limited by the lack of data regarding CT, it shows that RT is beneficial for patients with Stage II – IV GC. OS (months) in high grade vs. low grade disease. Stage Low Grade High Grade P-Value Patients with Surgical Resection IA 38 38 0.12 IB 34 29 <0.01 II 25 22 <0.01 IIIA 20 17 <0.01 IIIB 16 15 0.36 All Patients IV 6 5 <0.01