tbuckley/cabot-search huggingface dataset:
Network-based approach identifies SP1 as a common node in emphysema and lung cancer
Authors: Neil Kelly, Josiah Radder, Adriana Leme, Steven Shapiro
Journal: European Respiratory Journal (2014)

Introduction : Cigarette smoking is the major culprit behind emphysema and lung cancer development, yet their pathogeneses seem to have opposing molecular mechanisms. For example, VEGFR2 blockade is effective against lung cancer yet spurs emphysema in mice.  Objectives : Using protein interaction networks, we sought to identify a common node in the frequently comorbid conditions.  Methods : A global interactome of 12,760 nodes and 77,005 edges was constructed from data sets including protein-protein, transcription factor-target, kinase-substrate, and protease-substrate interactions. 105 emphysema proteins were identified from the literature, while 989 lung cancer proteins were taken from a list curated by the National Cancer Institute. A hypergeometric enrichment score based upon the number of edges connecting lung cancer proteins and an emphysema interactome was used to derive p-values.  Results : An emphysema interactome was constructed within the global network based upon the 105 emphysema proteins identified in the literature. Compared to 100,000 randomly generated networks of 105 nodes, the emphysema interactome contained 89 edges (random mean = 5.16, p  -7 ) and a largest connected component of 58 nodes (random mean = 3.54, p  -7 ) indicating a robust, connected network. Among lung cancer proteins, SP1 was the most connected with 16 edges to the emphysema interactome (p = 1.14 x 10 -12 ).  Conclusions : Our network-based analysis predicted SP1 to be a common node in lung cancer and emphysema. The SP1 inhibitor mithramycin is known to impede lung cancer progression in mice, and we are evaluating the effect of mithramycin on emphysema development in mice with results to be presented at the meeting.
Metastatic patterns in small-cell lung cancer: correlation of autopsy findings with clinical parameters in 537 patients.
Authors: J A Elliott, K Osterlind, F R Hirsch, H H Hansen
Journal: Journal of Clinical Oncology (1987)

Postmortem material from 537 patients included in various protocols of intensive combination chemotherapy or chemoradiotherapy for the management of small-cell anaplastic carcinoma of the lung (SCLC) has been reviewed. Patterns of residual or recurrent disease were analyzed in relation to pretreatment clinical parameters. Residual primary tumor (P less than .05), regional lymph node involvement (P less than .01), hepatic (P less than .01), bone (P less than .05), and renal metastases (P less than .05) were all significantly less frequent among patients with initially limited-stage disease compared with extensively staged patients. The frequency of residual intrathoracic tumor and metastatic pattern did not significantly differ between partial responders (PRs) and nonresponders (NRs). Patients with limited disease achieving a complete remission had a lower frequency of intrathoracic tumor (P less than .001) at autopsy compared with limited-stage PRs. However, for extensive-stage patients the pattern of residual disease was essentially independent of tumor response. Prior surgery was associated with a reduced burden of metastases only in those who underwent a radical resection. The addition of radiotherapy to the primary tumor and mediastinum failed to modify the autopsy distribution of residual tumor compared with that in patients treated with chemotherapy alone. Metastatic patterns were similar with or without prophylactic abdominal radiotherapy, while prophylactic cranial irradiation (PCl) did not prevent the development of cerebral metastases in patients whose systemic response to treatment was either partial or nonexistent. However, a beneficial effect of PCl in compete responders (CRs) was not excluded.
Toxicity and Efficacy of Defined Doses of CD4+ Donor Lymphocytes for Treatment of Relapse After Allogeneic Bone Marrow Transplant
Authors: Edwin P. Alyea, Robert J. Soiffer, Christine Canning, Donna Neuberg, Robert Schlossman, Christopher Pickett, Heather Collins, Yulan Wang, Kenneth C. Anderson, Jerome Ritz
Journal: Blood (1998)
An Ethical Dilemma: A nurse is suspended
Authors: J. M Kellett
Journal: BMJ (1996)

A nurse is suspended A day hospital sister was suspended and given afinalformal warningfor obeying the request of her consultant to give a patient tranquilising medication in disguise.Though a disciplinary inquiry exonerated the consultant, the action on the nurse has not been rescinded.This case questions the authority of the multidisciplinary team and the role of nursing managers.We asked two geriatricians andforensic scientists to comment on the case.
Repeatability of the endurance shuttle walk test in COPD
Authors: Shirley Ngai, Jennifer Alison, Lissa Spencer, Alice Jones
Journal: European Respiratory Journal (2012)

The aim was to evaluate the repeatability of the endurance shuttle walk test (ESWT) measured within the same day, within the same week and a week apart.

Methods: Individuals diagnosed with COPD were recruited. Participants were asked to perform two incremental shuttle walk tests (ISWT) for predicting the walking intensity for the ESWT. ESWT 1 (E1) and ESWT 2 (E2) were performed on the same day, 30 minutes apart. ESWT 3 (E3) was performed within a week from E2 and ESWT 4 (E4) was performed one week after E3. Heart rate (HR) (Polar RS800CX, Polar, Finland) and dyspnoea (Borg scale 0-10) were measured before and after each ESWT. Duration walked in each ESWT was measured and the corresponding walking distance was calculated. The repeatability of the four ESWTs was analyzed using repeated measures ANOVA.

Results: Twenty-two participants (mean ± SD age 71±6 years; FEV1% predicted 54 ±24%; TLC 122±21%) completed the study. The mean durations of E1 to E4 were 368±203s, 371±182s, 386±213s and 367±223s respectively, with no time effect (F= 0.18, p=0.79). The corresponding distances walked in E1 to E4 were 474±300m, 478±267m, 511±349m, 487±358m respectively, with no time effect (F=0.36, p=0.65). The percentage predicted HRmax at the end of E1 to E4 were 79±9 %, 80±11%, 82±9%, 80±9% respectively, with no significant time effect (F=1.94, p=0.13).

Conclusion: There was no evidence of a learning effect when an ESWT was repeated within one day, within one week or a week apart, showing that the ESWT is repeatable in people with moderate COPD.
Pulmonary rehabilitation: Investigating the characteristics and use of a warm-up
Authors: Elizabeth Heywood, Gill Phillips
Journal: European Respiratory Journal (2011)

Background:  Exercise training is recognised as an essential component of pulmonary rehabilitation (PR). Guidelines however do not detail a warm-up phase although evidence when prescribing any form of physical activity considers warming up as fundamental for optimal performance. Warm-up structure should relate to the subsequent tasks and consider individual capabilities. Particular attention is therefore required in PR that participants are warmed-up but not fatigued before exercise training.   Aims and objectives:  To investigate current practice in PR, considering specific characteristics and use of a warm-up phase.   Methods:  An online, prospective, cross-sectional survey using questionnaires disseminated through Physiotherapy networks in the UK.   Results:  All 52 respondents reported use of a warm-up. The majority included upper and lower limb movements integrated with low intensity aerobic exercise. Marching on the spot was the predominant activity reported but also thoracic rotations (23%), walking (12%) and lateral trunk flexion (14%). Stretching was integrated into all programmes. Warm-ups lasted between 6-10 minutes for 51% (range 3-15 minutes). Modified Borg Scale of Perceived Breathlessness was used by 12% to determine warm up intensity. However, 29% reported participants frequently failed to complete the warm-up, with 88% limited by breathlessness.   Conclusions:  All surveyed PR programmes report the inclusion of a warm-up phase though with considerable variability regarding content, duration, and intensity. Individuals however may fail to complete due to breathlessness. Further research is required to determine how warm-ups in PR can be effectively structured for maximum participant benefit.
Abstract 873: Going Beyond Obstructive Sleep Apnea Syndrome: The Relationship Between Daytime Sleepiness and Metabolic Syndrome in Mexican-American Women
Authors: Smriti Shivpuri, Paul J Mills, Linda C Gallo
Journal: Circulation (2009)

Background: Impaired sleep has been associated with decreased insulin sensitivity and increased blood pressure and sympathetic nervous system activity, which may contribute to the development of th...
Detection of specific mitochondrial RNA gene mutations in asthma patients: Contribution of haplogroup U
Authors: Foteini Malli, Emily Zifa, Konstantinos Gourgoulianis, Zissis Mamuris, Zoe Daniil
Journal: European Respiratory Journal (2011)

Background:  Maternal history of asthma is among the most consistently reported risk factors for asthma in children. Furthermore, a number of studies suggest that mitochondrial dysfunction plays a role in the pathogenesis of asthma. Until now, it was never investigated whether an implication of mitochondrial tRNA gene mutations exists in the genetics of bronchial asthma.   Methods:  To shed more light on the role of the mitochondrial genome in the etiology of asthma we analyzed the mitochondrial tRNA genes, and part of their flanking regions, in 26 unrelated patients with asthma and we compared the findings with a set of 60 healthy controls.   Results:  We found a total of 10 mutations in 19 out of 26 asthmatic patients. Four of the mutations (595insC in tRNA Phe , A8343G in tRNA Lys , T10448C in tRNA Arg  and G709A in 12S rRNA) were not found in the control group. Five mutations were observed in controls but in a significantly lower rate: 3.3%, vs. 27% (A12308G in tRNA Leu(CUN) ), 5% vs. 7.7% (G15928A in tRNA Thr ), 10% vs. 57.7% (A750G in 12S rRNA), 1.67% vs. 3.87% (T3197C in 16S rRNA and A15954C in MT-NC10). In the control group we did not observe any of the 9 combinations of mutations detected in asthma patients. We observed that 27% of the asthma patients (vs. 3% of the controls) belonged to the haplogroup U (characterized by the presence of A12308G and T7028C mutations), for which several studies already reported an association with atopic phenotypes.   Conclusions:  Mitochondrial tRNA and rRNA mutations are more frequent in asthma patients than controls. However, it is certain that further studies in larger cohorts are needed to confirm these observations.
Abstract 13130: The Blood Lactate Clearance Following Extracorporeal Cardiopulmonary Resuscitation for Pediatric Patients With In-Hospital Cardiac Arrest
Authors: Shuchien Huang, En-Ting Wu, Yih-Sharng Chen, Wen-Je Ko, ShoeiShen Wang
Journal: Circulation (2011)

Purpose: Post-cardiac arrest care after return of spontaneous circulation (ROSC) is important to improve the likelihood of patient survival. The blood lactate level has been recommended for monitor...
Abstract 2028: Anatomical Remodeling of the Left Atrium in Paroxysmal Atrial Fibrillation by Multislice Computed Tomography In Comparison with Chronic Atrial Fibrillation and Normal Sinus Rhythm
Authors: Koki Nakamura, Nobusada Funabashi, Masae Uehara, Hiroyuki Takaoka, Marehiko Ueda, Taichi Murayama, Yuzuru Mita, Fumiaki Maeda, Issei Komuro
Journal: Circulation (2007)

Purpose: Anatomical remodeling of the left atrium (LA) in subjects with paroxysmal atrial fibrillation (PAF), chronic atrial fibrillation (CAF) and normal sinus rhythm (NSR) was examined by multisl...
Guidelines for the management of adult lower respiratory tract infections - Summary
Authors: M. Woodhead, F. Blasi, S. Ewig, J. Garau, G. Huchon, M. Ieven, A. Ortqvist, T. Schaberg, A. Torres, G. van der Heijden, R. Read, T.J.M. Verheij
Journal: Clinical Microbiology and Infection (2011)
Association of Polymerase e–Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1
Authors: Brooke E. Howitt, Sachet A. Shukla, Lynette M. Sholl, Lauren L. Ritterhouse, Jaclyn C. Watkins, Scott Rodig, Elizabeth Stover, Kyle C. Strickland, Alan D. D’Andrea, Catherine J. Wu, Ursula A. Matulonis, Panagiotis A. Konstantinopoulos
Journal: JAMA Oncology (2015)

Immune checkpoint inhibitor therapy has shown benefit in various cancers, but their potential in endometrial cancer (EC) is unknown.Prediction of neoantigen load was performed using sequencing data from the Cancer Genome Atlas data set. Evaluation of tumor-infiltrating lymphocytes (TILs) and PD-1 and PD-L1 expression was performed in 63 patients with EC referred to our institution. The predicted median (range) neoantigen load (predicted neoepitopes per sample) was proportional to the mutational load: highest in ultramutated polymerase e (POLE) tumors (8342 [628-20 440]), less in hypermutated MSI (541 [146-8063]; P < .001), and lowest in microsatellite-stable tumors (70.5 [7-1877]; P < .001). The POLE and MSI ECs exhibited higher numbers of CD3+ (44.5 vs 21.8; P = .001) and CD8+ (32.8 vs 13.5; P < .001) TILs compared with microsatellite-stable tumors. PD-1 was overexpressed in TILs (81% vs 28%; P < .001) and peritumoral lymphocytes (90% vs 28%; P < .001) of POLE and MSI tumors. PD-L1 expression was infrequently noted in tumor cells but was common in intraepithelial immune cells and more frequent in POLE and MSI tumors (39% vs 13%; P = .02).Polymerase e-mutated and MSI ECs are associated with high neoantigen loads and number of TILs, which is counterbalanced by overexpression of PD-1 and PD-L1. Polymerase e-mutated and MSI EC tumors may be excellent candidates for PD-1-targeted immunotherapies.
Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study
Authors: Miguel O'Ryan, Ananda S Bandyopadhyay, Rodolfo Villena, Mónica Espinoza, José Novoa, William C Weldon, M Steven Oberste, Steve Self, Bhavesh R Borate, Edwin J Asturias, Ralf Clemens, Walter Orenstein, José Jimeno, Ricardo Rüttimann, Sue Ann Costa Clemens
Journal: The Lancet Infectious Diseases (2015)
Regulating e-cigarettes to help them realise their potential as an anti-smoking tool
Authors: Lawrence O Gostin
Journal: BMJ (2015)

Gornall’s article captures the substance and passion of the controversy over e-cigarettes.1 But debates over exactly how harmful e-cigarettes are and about their role in smoking cessation or youth nicotine initiation are an unnecessary distraction and a harmful diversion.

Lindblom suggests that, on the basis of what is already known, it would …
Use of Hypnosis in Criminology: Discussion Paper
Authors: David Waxman
Journal: Journal of the Royal Society of Medicine (1983)

Memories of events which are unremarkable may pass unrecorded or may fade with the passage of time. In any situation of stress, anxiety may cloud the memory of the incident and in the case of some intensely frightening or humiliating experience such material may not be subject to voluntary conscious recall and may be repressed. A technique for uncovering certain ‘forgotten’ or repressed memories with the use of hypnosis is described. A similar method has been used in order to retrieve such memories in the investigation of witnesses and victims of serious crime. Nevertheless, various aspects of the overall validity of such a procedure have been called into question and for this reason the results of numerous experiments and the conclusions arrived at in many papers are discussed. It is emphasized that a rigid code of conduct be followed if hypnosis is to be used as an investigatory tool.
Correlates of high levels of use of short-acting beta agonists in asthma
Authors: Laurent Laforest, Jennifer Martin, Idlir Licaj, Gilles Devouassoux, Gérard Chatte, Mélanie Broquet, Eric Van Ganse
Journal: European Respiratory Journal (2011)

Background:  High use of short-acting beta agonists (SABAs) may reflect potential risks in asthma management. A better understanding of the characteristics of high users of SABAs is critical to improve quality of care.   Objectives:  To describe asthma patients with high levels of use of SABA, including their characteristics and medical resource utilisation.   Methods:  A random sample of patients aged 16-40, with regular use of dispensed respiratory drugs (R03, ATC classification) in 2005 was selected from the French claims database (EGB). Asthma-related hospital admissions were retrieved. Patterns of use of SABAs in 2007 were described. The correlates (baseline characteristics and asthma-related variables) of using ≥ 12 SABA units in 2007 were identified.   Results:  Among 2093 patients (median age = 33 year-old, 54% females), 65% were using SABAs in 2007 and 8% used ≥ 12 units during this period. These patients were more likely to have a long-term disease status (p   Conclusions:  Many patients are still using high levels of SABAs and are possibly at risk of exacerbations. The reasons of this high use of rescue medication require a better understanding.
Zinc and zinc transporters in human alveolar and THP-1 macrophages and roles in phagocytosis/efferocytosis
Authors: Peter Zalewski, Rhys Hamon, Hai Tran, Hubertus Jersmann, Sandra Hodge, Mariea Bosco
Journal: European Respiratory Journal (2014)

Impaired efferocytic clearance of apoptotic epithelial cells by alveolar macrophages (AM) occurs in chronic obstructive pulmonary disease (COPD) and leads to a pro-inflammatory state. Zinc (Zn) deficiency in mice exacerbates lung inflammation and results in an accumulation of apoptotic epithelial cells. Zn may be an important factor in monocyte/macrophage differentiation and efferocytosis. Concentrations of Zn were significantly reduced in the bronchoalveolar lavage (BAL) of patients with COPD who are current smokers. BAL Zn was positively correlated with AM efferocytic ability and there was decreased efferocytosis in in vitro Zn depleted AM. In human THP-1 cells, monocyte differentiation to macrophages was accompanied by an 8-fold increase in cytosolic Zn, 41-fold and 26-fold increases in mRNA levels for two SLC30A Zn transporters ZnT3 and ZnT4, respectively, and smaller increases in several SLC39A Zn transporters (including ZIP1, ZIP13 and ZIP14). In Zn depleted macrophages, the only increase (32-fold) was in the SLC39A Zn transporter ZIP2. ZIP1 and ZIP14 were localized to the plasma membrane while ZIP2 was localized to the cytoplasm, perinuclear region and nucleoli. ZnT3 and ZnT4 were predominantly in intracellular vesicles although ZnT4 was also found in the trans-Golgi, where it is likely involved in incorporation of Zn into metalloproteins. Finally, macrophages of mice with knockout of ZIP1 had significantly reduced intracellular Zn and efferocytosis capability. We propose that Zn homeostasis in macrophages involves the coordinated action of several Zn transporters and that these play important roles in macrophage differentiation, efferocytosis and cell survival.
"DELAY" (PAVLOV) IN HUMAN PHYSIOLOGY
Authors: MAX LEVIN
Journal: American Journal of Psychiatry (1946)

When a person, eager to give expression to an impulse, restrains himself till an opportune moment (for example, a runner awaiting the start of a race), one is dealing with an experiment of Nature which duplicates, in principle, Pavlov's experiments on "delay." Excitations are roused by a conditioned stimulus but are held in check by inhibitions pending arrival of the proper moment. The sleepiness which man and lower animal alike sometimes show under these conditions signifies that the inhibitions have, so to speak, overshot the mark and have irradiated widely over the cerebral cortex.
Abstract 20145: ST2 and the Risk of CV Death or Heart Failure in Patients with Non-ST elevation Acute Coronary Syndromes (NSTE-ACS): Observations from MERLIN-TIMI 36
Authors: Marc P Bonaca, Anastacia Kudinova, Rahul Kakkar, Benjamin S Scirica, Marc S Sabatine, Sabina A Murphy, Eugene Braunwald, Richard T Lee, David A Morrow
Journal: Circulation (2010)
The treatment of recurrent brain metastases with stereotactic radiosurgery.
Authors: J S Loeffler, H M Kooy, P Y Wen, H A Fine, C W Cheng, E G Mannarino, J S Tsai, E Alexander
Journal: Journal of Clinical Oncology (1990)

Between May 1986 and August 1989, we treated 18 patients with 21 recurrent or persistent brain metastases with stereotactic radiosurgery using a modified linear accelerator. To be eligible for radiosurgery, patients had to have a performance status of greater than or equal to 70% and have no evidence of (or stable) systemic disease. All but one patient had received prior radiotherapy, and were treated with stereotactic radiosurgery at the time of recurrence. Polar lesions were treated only if the patient had undergone and failed previous complete surgical resection (10 patients). Single doses of radiation (900 to 2,500 cGy) were delivered to limited volumes (less than 27 cm3) using a modified 6MV linear accelerator. The most common histology of the metastatic lesion was carcinoma of the lung (seven patients), followed by carcinoma of the breast (four patients), and melanoma (four patients). With median follow-up of 9 months (range, 1 to 39), all tumors have been controlled in the radiosurgery field. Two patients failed in the immediate margin of the treated volume and were subsequently treated with surgery and implantation of 125I to control the disease. Radiographic response was dramatic and rapid in the patients with adenocarcinoma, while slight reduction and stabilization occurred in those patients with melanoma, renal cell carcinoma, and sarcoma. The majority of patients improved neurologically following treatment, and were able to be withdrawn from corticosteroid therapy. Complications were limited and transient in nature and no cases of symptomatic radiation necrosis occurred in any patient despite previous exposure to radiotherapy. Stereotactic radiosurgery is an effective and relatively safe treatment for recurrent solitary metastases and is an appealing technique for the initial management of deep-seated lesions as a boost to whole brain radiotherapy.