tbuckley/cabot-search huggingface dataset:
Current social stressors and symptoms of depression
Authors: Frederic W. Ilfeld
Journal: American Journal of Psychiatry (1977)

The author explores the relationship of current social stressors (cirumstances of daily social roles that are generally considered problematic or undesirable) to depressive symptoms. Subjects were 2,299 adults aged 18-65 in the Chicago area. Over a fourth of the variance in depressive symptoms is accounted for by five social stressors. Depression is most closely related to the social stressors of marriage and parenting, and symptoms increase proportionately to the total number of stress areas. These data suggest that a focus on intervention and prevention in areas of family and marital life is desirable.
Induction of autophagy improves hepatic lipid metabolism in glucose-6-phosphatase deficiency
Authors: Benjamin L. Farah, Dustin J. Landau, Rohit A. Sinha, Elizabeth D. Brooks, Yajun Wu, Suet Yin Sarah Fung, Tomohiro Tanaka, Masahiro Hirayama, Boon-Huat Bay, Dwight D. Koeberl, Paul M. Yen
Journal: Journal of Hepatology (2015)
“Vertical” Inhibition of HER2 Yields Horizontal Gains in the Clinic
Authors: George W. Sledge, Mark D. Pegram
Journal: Clinical Cancer Research (2015)

Abstract HER2-targeted therapy has moved beyond trastuzumab to include other monoclonals targeting the cell surface, receptor tyrosine kinase inhibitors of HER2, and antibody–drug conjugates. Afatinib, a small molecule receptor tyrosine kinase inhibitor, now joins the ranks of HER2-targeting agents in combination with trastuzumab. The combination brings new opportunities and challenges. Clin Cancer Res; 21(12); 2663–5. ©2015 AACR. See related article by Ring et al., p. 2737
The German severe asthma register
Authors: Stephanie Korn, Marisa Hübner, Karl-Christian Bergmann, Antje Jahn, Peter Kardos, Andrea Koch, Marek Lommatzsch, Eckhard Hamelmann, Roland Buhl
Journal: European Respiratory Journal (2012)

Patients with severe persistent asthma represent the highest unmet medical need among the asthmatic population today. To improve the understanding of more severe disease progresses in pediatric and adult asthma the German Asthma Net (GAN e.V.) launched a National Severe Asthma Register in December 2011. Enrolled patients undergo detailed clinical and physiologic evaluations, including patients9 medical history, allergy, lung function, lung inflammation, blood testing as well as past and concomitant medication and comorbidities. As of February 20, 2012 six participating centers joined the program and recruited 93 subjects (mean age±SEM 49±1 years, 63% female, FEV1 2.0±0.1 L (65.3±2.1%), 97% uncontrolled or partly controlled asthma according to GINA, 54% allergic asthma, 46% on oral corticosteroids, 39% on omalizumab, eNO 51±6 ppb, 3.4±0.4 exacerbations during the last 12 months). Recruitment of a larger number of subjects with severe asthma, including children, is ongoing and will allow further characterization of clinical, physiologic, cellular and biochemical factors related to severe disease in a longitudinal assessment to identify parameters that improve diagnosis, phenotyping, management and treatment of this heterogeneous condition. In addition, the German Severe Asthma Register may help to confirm and extend results obtained in similar databases, including U-BIOPRED and SARP.
Cardiopulmonary Resuscitation Training Revisited
Authors: A P L Goodwin
Journal: Journal of the Royal Society of Medicine (1992)

The cardiopulmonary resuscitation (CPR) skills of 50 junior hospital doctors (22 house officers and 28 senior house officers) were assessed. Theoretical knowledge was measured by a multiple choice questionnaire and practical ability with the Laerdal Skillmeter Resusci Anne. Only 40% of the study group passed both tests. Those doctors who had previously received regular CPR training performed better in the practical test (P<0.05) than those who had not. Theoretical knowledge was unrelated to previous CPR training. It is recommended that junior hospital doctors should undergo regular CPR training every 6 months, in order to maintain their practical CPR skills.
Fine Needle Aspiration Biopsy in Diagnosis of Metastases to Thyroid Gland
Authors: Thomas W J Lennard, Viney Wadehra, John R Farndon
Journal: Journal of the Royal Society of Medicine (1984)

Three cases of metastasis to the thyroid gland are reported, in each of which fine needle aspiration biopsy confirmed the diagnosis and obviated the need for surgery. Fine needle aspiration biopsy is able to confirm suspected intrathyroid metastasis and can be performed as an outpatient or bedside procedure.
Dosing regimen of granulocyte-macrophage colony-stimulating factor to support dose-intensive chemotherapy.
Authors: J A Neidhart, A Mangalik, C A Stidley, S L Tebich, L E Sarmiento, J E Pfile, D H Oette, F B Oldham
Journal: Journal of Clinical Oncology (1992)

PURPOSE This trial evaluated the optimum dosing regimen for recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) to support a dose-intensive chemotherapy regimen given without progenitor cell replacement. PATIENTS AND METHODS Fifty-one patients with refractory malignancy received cyclophosphamide 2,500 mg/m2 on days 1 and 2, etoposide 500 mg/m2 on days 1, 2, and 3, and cisplatin 50 mg/m2 on days 1, 2, and 3. Patients were hospitalized from cycle days 1 to 4 for chemotherapy and readmitted for cytopenic temperatures above 38.5 degrees C. Cycles were repeated every 35 days in patients who responded to a total of three cycles. GM-CSF was given at doses of 250 to 1,000 micrograms/m2 by continuous intravenous infusion (CIV) or subcutaneously starting on cycle days 3 to 6. Two nonrandomized control groups are used. RESULTS The optimum regimen of GM-CSF for shortening the duration of leukopenia (WBC count less than 300/microL) was 500 micrograms/m2 given CIV. Duration of leukopenia was 5.9 days compared with 13.2 and 10.2 days in the controls (P less than .05). The optimum regimens for shortening duration of hospitalization, however, were 500 and 750 micrograms/m2/d given as divided (twice daily) subcutaneous injections. Durations of hospitalization were 9.6 and 9.8 days compared with 15.7 and 22.2 days in the controls (P less than .08). At the higher GM-CSF dose, only 36% of patients required readmission for cytopenic fever. Toxicities of GM-CSF at clinically useful doses were minimal. Twelve patients had complete response (24%) and 22 partial response (43%). CONCLUSIONS This dose-intensive regimen can be given safely without progenitor replacement. rhu GM-CSF decreases the duration of severe leukopenia and decreases the need for hospitalization and antibiotic therapy.
Association between high tumor CCL2 expression and poor survival in patients with resectable pancreatic cancer
Authors: L. Yan, Y. Hu, M. R. D’Andrea, M. A. Towers, Y. Wang, P. Kesavan, M. DeWitte, M. T. Nakada, S. Ahrendt
Journal: Journal of Clinical Oncology (2007)

4618 Background: CCL2 (MCP-1) is a chemoattractant protein highly expressed in a variety of cancer types. The expression level of CCL2 has been linked to aggressive disease progression, early dissemination, and poor survival in certain cancers. Therefore, we assessed the potential association between CCL2 expression and patient prognosis in pancreatic cancer. Methods: Cylindrical tissue cores from a large retrospective, nonrandomized series covering 133 patients with resected pancreatic cancer were used to build a tissue microarray. CCL2 expression was determined using immunohistochemistry. Results: High intratumoral CCL2 expression and low intratumoral CCL2 expression were present in 44 (33%) and 89 (67%) tumors, respectively. Kaplan-Meier median survival among patients with low intratumoral CCL2 expression (19.1 months) was longer than that among those with high CCL2 expression (12.1 months). In multivariate analysis, more advanced pathological stage [risk ratio (RR) = 1.57; P = 0.038], poorly differentiated histology (RR = 1.68; P = 0.019), and high CCL2 expression [RR = 1.62; 95% confidence interval (CI) = 1.05–2.49; P = 0.028] were independent predictors of mortality. Conclusions: High CCL2 expression is a marker of poor prognosis in resected pancreatic cancer. [Table: see text]
Interleukin-7 Upregulates the Interleukin-2–Gene Expression in Activated Human T Lymphocytes at the Transcriptional Level by Enhancing the DNA Binding Activities of Both Nuclear Factor of Activated T Cells and Activator Protein-1
Authors: Sonja I. Gringhuis, Lou F.M.H. de Leij, Emmy W. Verschuren, Peter Borger, Edo Vellenga
Journal: Blood (1997)
Poly(I:C)-induced responses in nasal and bronchial epithelial cells of patients with asthma and healthy controls
Authors: A.H. Wagener, S. Luiten, L.N. Venekamp, P.W. Kunst, P.J. Sterk, C.M. van Drunen
Journal: European Respiratory Journal (2011)

Rationale:  The majority of asthmatic exacerbations is associated with respiratory virus infection (Busse, Lancet 2010). Since airway epithelium is the primary site of a viral entry, we hypothesized that nasal and bronchial epithelium are equally responsive to respiratory viruses when measured as cytokine responses to poly(I:C).   Aim:  We compared baseline cell activity and induced responses of primary human nasal and bronchial epithelial cells to poly(I:C) in allergic asthmatics and healthy controls.   Materials and method:  This was a 2-group study in 8 allergic asthmatics (defined by GINA, PC 20    Results:  There were no significant between-group or between-upper and lower airway differences in baseline cell activity. Exposure to poly(I:C) induced up-regulation of several cytokines with no significant between-group differences. Asthmatics showed a higher activity for MIP-1b (p=0.009), MIP-1a (p=0.003), MCP-1 (p=0.038), and TNF-α (p=0.05) in nasal as compared to bronchial epithelial cells.   Conclusion:  Expression is highly variable in individual subjects, and asthmatics demonstrate higher expression for MIP-1b, MIP-1a, MCP-1 and TNF-α in nasal  versus  bronchial epithelial cells after stimulation with poly(I:C). Our findings suggest that nasal and bronchial epithelium exhibit differential responses to double-stranded RNA, and thereby to viral infection.
Abstract 13735: CD4+ T-lymphocytes Modulate Wound Healing After Experimental Myocardial Infarction In Mice
Authors: Ulrich Hofmann, Niklas Beyersdorf, Johannes Weirather, Georg Ertl, Thomas Kerkau, Stefan Frantz
Journal: Circulation (2010)

Background: Activation and contribution of innate immune cells to myocardial ischemia-reperfusion injury, wound healing and remodelling has been studied in great detail. However, the role of the ad...
Ethics, Interrogation, and the American Psychiatric Association
Authors: Paul Summergrad, Steven S. Sharfstein
Journal: American Journal of Psychiatry (2015)

Recently, it has been alleged that the American Psychological Association colluded with the George W. Bush administration to allow psychologist participation in enhanced interrogations of detainees in the war on terror.James Risen writing in The New York Times (1) asserted that a recent review of emails suggests that the American Psychological Association policy that supported this interrogation was adopted with the direct involvement of psychologists who worked in the U.S. national security apparatus and structured to overcome objections from the Office of Legal Counsel in the Department of Justice over the continuation of the enhanced interrogation program.The American Psychological Association Board of Directors in late 2014 announced an independent legal review of these allegations to be overseen by a special committee of their board (2).These reports led us to review the history of the adoption in 2006 of the formal position of the American Psychiatric Association that states categorically that psychiatrists should not participate in such enhanced interrogations (3).Sharfstein served as President of the American Psychiatric Association in 2005-2006 when the position statement was written and adopted; Summergrad served as President in 2014-15 when these new allegations regarding the American Psychological Association arose, and worked to make the American Psychiatric Association's long-standing opposition to psychiatrist involvement in interrogations clear to the general public (4).Looking back on the 2005-2006 period, the question of whether physicians, especially psychiatrists, were participating in the interrogation of detainees had become a particular focus of concern at the Guantanamo Naval Base in Cuba in 2005.Concerns about national security and possibility that enhanced interrogation might foil further terrorist attacks seemed to take priority over other concerns.
ATDC/TRIM29 Drives Invasive Bladder Cancer Formation through miRNA-Mediated and Epigenetic Mechanisms
Authors: Phillip L. Palmbos, Lidong Wang, Huibin Yang, Yin Wang, Jacob Leflein, McKenzie L. Ahmet, John E. Wilkinson, Chandan Kumar-Sinha, Gina M. Ney, Scott A. Tomlins, Stephanie Daignault, Lakshmi. P. Kunju, Xue-Ru Wu, Yair Lotan, Monica Liebert, Mats E. Ljungman, Diane M. Simeone
Journal: Cancer Research (2015)

Abstract Bladder cancer is a common and deadly malignancy but its treatment has advanced little due to poor understanding of the factors and pathways that promote disease. ATDC/TRIM29 is a highly expressed gene in several lethal tumor types, including bladder tumors, but its role as a pathogenic driver has not been established. Here we show that overexpression of ATDC in vivo is sufficient to drive both noninvasive and invasive bladder carcinoma development in transgenic mice. ATDC-driven bladder tumors were indistinguishable from human bladder cancers, which displayed similar gene expression signatures. Clinically, ATDC was highly expressed in bladder tumors in a manner associated with invasive growth behaviors. Mechanistically, ATDC exerted its oncogenic effects by suppressing miR-29 and subsequent upregulation of DNMT3A, leading to DNA methylation and silencing of the tumor suppressor PTEN. Taken together, our findings established a role for ATDC as a robust pathogenic driver of bladder cancer development, identified downstream effector pathways, and implicated ATDC as a candidate biomarker and therapeutic target. Cancer Res; 75(23); 5155–66. ©2015 AACR.
Calcium signaling in cilia and ciliary-mediated intracellular calcium signaling: Are they independent or coordinated molecular events?
Authors: Anatoliy I. Masyuk, Sergio A. Gradilone, Nicholas F. LaRusso
Journal: Hepatology (2014)

Abstract Primary cilia are solitary, non-motile extensions of the centriole found on nearly all nucleated eukaryotic cells between cell divisions. Only ˜200-300 nm in diameter and a few micrometers long, they are separated from the cytoplasm by the ciliary neck and basal body. Often called sensory cilia, they are thought to receive chemical and mechanical stimuli and initiate specific cellular signal transduction pathways. When activated by a ligand, hedgehog pathway proteins, such as GLI2 and smoothened (SMO), translocate from the cell into the cilium. Mutations in primary ciliary proteins are associated with severe developmental defects. The ionic conditions, permeability of the primary cilia membrane, and effectiveness of the diffusion barriers between the cilia and cell body are unknown. Here we show that cilia are a unique calcium compartment regulated by a heteromeric TRP channel, PKD1L1-PKD2L1, in mice and humans. In contrast to the hypothesis that polycystin (PKD) channels initiate changes in ciliary calcium that are conducted into the cytoplasm, we show that changes in ciliary calcium concentration occur without substantially altering global cytoplasmic calcium. PKD1L1-PKD2L1 acts as a ciliary calcium channel controlling ciliary calcium concentration and thereby modifying SMO-activated GLI2 translocation and GLI1 expression. Abstract A primary cilium is a solitary, slender, non-motile protuberance of structured microtubules (9+0) enclosed by plasma membrane. Housing components of the cell division apparatus between cell divisions, primary cilia also serve as specialized compartments for calcium signaling and hedgehog signaling pathways. Specialized sensory cilia such as retinal photoreceptors and olfactory cilia use diverse ion channels. An ion current has been measured from primary cilia of kidney cells, but the responsible genes have not been identified. The polycystin proteins (PC and PKD), identified in linkage studies of polycystic kidney disease, are candidate channels divided into two structural classes 11-transmembrane proteins (PKD1, PKD1L1 and PKD1L2) remarkable for a large extracellular amino terminus of putative cell adhesion domains and a G-protein-coupled receptor proteolytic site, and the 6-transmembrane channel proteins (PKD2, PKD2L1 and PKD2L2; TRPPs). Evidence indicates that the PKD1 proteins associate with the PKD2 proteins via coiled-coil domains. Here we use a transgenic mouse in which only cilia express a fluorophore and use it to record directly from primary cilia, and demonstrate that PKD1L1 and PKD2L1 form ion channels at high densities in several cell types. In conjunction with an accompanying manuscript, we show that the PKD1L1-PKD2L1 heteromeric channel establishes the cilia as a unique calcium compartment within cells that modulates established hedgehog pathways.
Serial Imaging Changes During Treatment of Immunoglobulin G4–Related Disease With Multiple Pseudotumors
Authors: Kenya Kusunose, Junko Hotchi, Yuriko Takagawa, Susumu Nishio, Takayuki Ise, Takeshi Tobiume, Koji Yamaguchi, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata
Journal: Circulation (2015)
Features of asthma treatment while pregnancy
Authors: Svetlana Melnik, Olga Lavrova, Yulia Dymarskaya
Journal: European Respiratory Journal (2014)

Introduction: Now Budesonide (Bu) is considered to be a unique medication of B safety group by FDA criteria, to be used in pregnants with persistent asthma as it was marked at GINA-2007. Same time the amount of pregnants with asthma controlled by Fluticasone/Salmeterol (Fl/S) or Budesonide/Formoterol (Bu/F) before pregnancy increases. Also it is considered that treatment, administered before pregnancy may be continued during pregnancy if the patients asthma was well controlled with the medication before pregnancy.  The goal of the study was the comparison pregnancy duration, delivery and weight ratio of newborns in females with different severity of Asthma duration and various basic therapies.  Materials and methods: Study group contributed 1010 Asthmatic females aged 17 - 43 years, followed up by our staff together with gynecologists since early terms of their pregnancy.  Results: The frequency of gestational hypertension in patients, treated with Fl/S was significantly lower in comparison with Bu treated patients (p=0,028). Frequency of Caesarian section was significantly higher in Bu treated females in comparison with females, treated with Bu/F (p=0,02). Average weight ratio of kids born by females with severe Asthma was lowest in patients with severe Asthma, who were administered Bu (2895,6±189,9). Average weight value of kids, born by Fl/S administered females (3516,7±94,1), was above median value of Asthmatic females in total (3346,1±99,4).  Conclusions: the combination of a LABA and an ICS is the preferred therapy in the cases of moderate and severe asthma in pregnants.
Clinical characteristics of acute asthma presentation to the emergency department
Authors: Rodolfo Ferrari, Fabrizio Giostra, Mario Cavazza
Journal: European Respiratory Journal (2011)

Background:  The incidence and complexity of asthma acute exacerbations (AA) are widely increasing. The emergency physician (EP) plays a key role in AA: emergency management; medical treatment; diagnosis; prevention; maintenance; follow up; education about self-management.   Aims:  To define the epidemiological and clinical impact of AA at presentation to the emergency department (ED) and the role of the EP.   Methods:  Six months observational prospective clinical study including every consecutive AA patient who presented to the ED of a university teaching hospital   Results:  Patients: 209 (1.15/day).  Rates%: females 63.5; Italian 70.2; practitioner9s request 6.0; current therapy for asthma 83.1; known risk factors 63.5; previous physician9s visit 15.9; ED therapy 79.5; ED mechanical ventilation 2.9; hospitalization 18.2; discharge therapy 77.9; discharge follow up 65.9; ED rebounds 4.3.  Media: age 41 years; ED waiting time 48 minutes; ED time for evaluation and treatment 104 minutes; ED total time 153 minutes; systolic blood pressure 127 mmHg; diastolic 78 mmHg; pulse rate 94 bpm; pulsoxymetry 97%; body temperature 36.9°C; symptoms debut before ED 7 days; time between second and first ED visit 50 days.   Conclusions:  The majority of asthma exacerbations has a window of opportunity in which deterioration can be recognized and reverted; severe asthma attacks can be prevented by currently available strategies. Of concern was the dependence of most patients on ED for initial care, and the small number of cases in which patients visited a physician before presenting to the hospital. Nowadays the EP must be involved in approaching all typical most frequent and relevant causes of inadequate asthma control.
Orthopaedic Operations: Variation in Case-Mix over a 10-Year Period
Authors: Keith Williams
Journal: Journal of the Royal Society of Medicine (1986)

The variation in case-mix of patients admitted for routine (non-emergency) orthopaedic surgery at a Staffordshire orthopaedic hospital over a 10-year period was studied, with the aid of the BUPA Schedule of Surgical Procedures. Over this period there was a 2% decrease in the total number of operations performed. There was a marked reduction in the number of 'minor' operations performed, and a marked increase in the number of 'major' and more complex operations performed. The overall workload, as judged by estimated surgeons' fees, rose by 43%. This study offers clear support to the claim that the complexity of orthopaedic operations performed has significantly increased over a ten-year period.