tbuckley/cabot-search huggingface dataset:
Can IASLC/ATS/ERS subtype help predict response to chemotherapy in small biopsies of advanced lung adenocarcinoma?
Authors: Gregory J. Riely, William D. Travis
Journal: European Respiratory Journal (2014)

The identification of somatic EGFR mutations and ALK gene rearrangements has dramatically changed our understanding of the biology of lung cancers and provided extraordinarily helpful predictive biomarkers that allow physicians to determine which patients will have the greatest likelihood of benefit with certain targeted therapies. These predictive biomarkers allow rational use of the targeted therapies appropriate for the individual driver oncogene (erlotinib, gefitinib, and afatinib for EGFR mutant cancers, and crizotinib for ALK rearranged cancers). There are even some indications that these mutations predict for better outcomes with some standard chemotherapy [1, 2]. Despite this, the majority of patients either have no identifiable driver oncogene or it is one without an associated effective therapy ( e.g. KRAS mutation). For these patients, it is challenging to decide which therapy should be given. The difficulty arises from the poor response rates for conventional chemotherapy regimens, with just 30–35% of patients having significant tumour shrinkage with state-of-the art first line platinum-based chemotherapy regimens. Clearly, there is a desperate need for further insight into therapy choices and biology for the majority of patients with lung adenocarcinomas.

In this issue of European Respiratory Journal , Campos-Parra et al. [3] present findings that suggest that using the approach to predominant pathological subtyping proposed in the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification of lung adenocarcinoma in patients with advanced disease may predict outcomes after standard chemotherapy. …
The declined CD4+ CD25+Treg cells in patients with moderate to severe asthma associated with over-expressed Th2 response
Authors: Yuheng Shi, Guochao Shi
Journal: European Respiratory Journal (2012)

Background  Recent studies have showed that Th2 cells can induce the apoptosis of CD4+ CD25+ Treg cells or resist the immunosuppressive effect of Treg cells. We hypothesize that an imbalance of Th2/Treg is presented in patients with allergic asthma.  Methods  Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. The proportions of peripheral blood CD4+CD25+ Treg cells and Th2 cells were determined by flow cytometry. The concentration of IL-10, TGF-β and IL-4 in plasma was determined by ELISA. The expression of Foxp3 and GATA-3 mRNA in PBMCs from asthmatic patients and healthy donors was detected by RT-PCR.  Results  Compared with healthy donors and patients with mild asthma, the frequency of CD4+CD25+ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. There was no difference of Foxp3 mRNA expression among three groups. However, the frequency of Th2 cells, IL-4 levels and expression of GATA-3 mRNA was higher in patients with mild and moderate to severe asthma than in the control group. The ratio of Th2/Treg and their cytokines was increased in allergic asthma, especially for moderate to severe asthma. The ratio of GATA-3/Foxp3 mRNA was increased in allergic asthma. In patients with moderate to severe asthma, the frequency of peripheral blood Treg cells was negatively correlated to the percentage of Th2 cells and IL-4 levels.  Conclusions  The decline of Treg cells in patients with moderate to severe asthma may play an important role in progress of the disease.
Surveillance for AIDS in a Central African City
Authors: Jonathan M. Mann, Henry Francis, Thomas Quinn, Pangu Kaza Asila, Ngaly Bosenge, Nzila Nzilambi, Kapita Bila, Muyembe Tamfum, Kalisa Ruti, Peter Piot, Joseph McCormick, James W. Curran
Journal: JAMA (1986)

Surveillance for acquired immunodeficiency syndrome (AIDS) in Kinshasa, Zaire, was initiated in July 1984, using a modified version of the case definition developed by the Centers for Disease Control. During the first eight months, 332 patients met all clinical and laboratory criteria; surveillance information was available for 295 (89%) of these patients. Of the sera tested from these patients, 99% had antibodies to human T-cell lymphotropic virus type III/lymphadenopathy-associated virus by both enzyme-linked immunosorbent assay and Western blot procedures. The male-female case ratio was 1:1.1; the mean age of patients was 33.6 years (median, 32 years; range, 1.5 to 64 years); and men were significantly older than women (mean, 37.4 vs 30.0 years). The estimated incidence rate for adults in Kinshasa is 380 cases per 1 million people per year. Peak age-specific incidence rates for men and women occurred among the 30- to 39-year age group, although the rate for men in this age group was 24% higher than the rate for women (786 vs 601 per 1 million). A reasonable estimate of the current annual incidence of AIDS is 550 to 1,000 cases per 1 million people. Surveillance of AIDS in Zaire provides important information on transmission patterns and rates in Africa.
A CONSIDERATION OF THE NEED OF BETTER PROVISION FOR THE TREATMENT OF MENTAL DISEASE IN ITS EARLY STAGE
Authors: J. Montgomery Mosher
Journal: American Journal of Psychiatry (1909)

a pavilion for the treatment of mental diseases to which patients might be admitted without formality and with the same freedom as those received in the wards for the sick and injured.It was proposed to meet the needs of certain cases of incipient or transitory mental disturbance for which no provision was otherwise made.If insanity threatened it was the practice in Albany, as elsewhere, to temporize until symptoms developed requiring judicial consideration, when TREATMENT OF MENTAL DISEASE IN ITS EARLY STAGE [Jan. the representative medical body of another state, but because Pennsylvania is pre-eminent in medical science and in progress in the care of the insane.It may not be out of place to recall that the first and oldest hospital of this country, the Pennsylvania Hospital in Philadelphia, obtained its charter mainly on the representations in the petition therefor, of the needs of persons "Distemper'd in Mind and depriv'd of their rational Faculties," and it is noteworthy that at that early day, 1751, the pathological nature of insanity was recognized in the effort to provide a hospital for "the cure and treatment of lunaticks," in order that "they may be restored to reason 1909
Gastrointestinal Complications of Dual Antiplatelet Therapy
Authors: Neelima G. Vallurupalli, Samuel Z. Goldhaber
Journal: Circulation (2006)

ase presentation: A 59-yearold man with a history of hypertension, dyslipidemia, and smoking was hospitalized with acute coronary syndrome requiring emergency percutaneous coronary intervention with 4 drug-eluting stents.His discharge medications included dual antiplatelet therapy with aspirin 325 mg/d and clopidogrel 75 mg/d.Three weeks after discharge, he returned to the Emergency Department with bloody stools and a hematocrit of 23% (previously 36%) and required 3 U of packed red blood cells.Endoscopy showed a bleeding duodenal ulcer with adherent clot (Figure).
Within-subject variability of tuberculosis immune responses in health care workers
Authors: Felix C. Ringshausen, Heiko Knoop, Stephan Schlösser, Gerhard Schultze-Werninghaus, Gernot Rohde, Albert Nienhaus
Journal: European Respiratory Journal (2011)

Background:  Although IFN-γ release assays (IGRAs) are increasingly used for periodic tuberculosis (TB) screening of health care workers (HCWs), data regarding the interpretation of IGRA results in serial testing is scare.   Objective:  To evaluate the within-subject variability of two commercial IGRAs, QuantiFERON®-TB Gold In-Tube (QFT) and T-SPOT®. TB  (T-SPOT).   Methods:  Thirty-four immunocompetent German HCWs (age 42±10 yrs, 79% female) without recent TB exposure or other individual risk factors were repeatedly tested with both IGRAs in weekly intervals over a four week period.   Results:  According to the manufacturers9 predefined dichotomous cut-offs 10 (29.4%) and 3 (8.8%) of the 34 subjects had divergent overall trends with the QFT and the T-SPOT, respectively (p   Conclusions:  We observed considerable variability with both IGRAs and a tendency towards regression of IGRA results over a 4-week period, which should be considered when interpreting repeated IGRA results.
Polymorphisms in the NOS1APGene Modulate QT Interval Duration and Risk of Arrhythmias in the Long QT Syndrome
Authors: Marta Tomás, Carlo Napolitano, Luciana De Giuli, Raffaella Bloise, Isaac Subirana, Alberto Malovini, Riccardo Bellazzi, Dan E. Arking, Eduardo Marban, Aravinda Chakravarti, Peter M. Spooner, Silvia G. Priori
Journal: Journal of the American College of Cardiology (2010)
Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection
Authors: K. Blondeau, V. Mertens, B. A. Vanaudenaerde, G. M. Verleden, D. E. Van Raemdonck, D. Sifrim, L. J. Dupont
Journal: European Respiratory Journal (2007)

Acid gastro-oesophageal reflux (GOR) and gastric aspiration have been labelled as risk factors for chronic rejection bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). The present study aimed to further characterise GOR (both acid and nonacid) and the degree of gastric aspiration in LTx recipients both with and without BOS. Impedance-pH recordings were used for GOR detection. Pepsin and bile acid levels were measured in bronchoalveolar lavage fluid (BALF). A total of 48% of patients had increased GOR, of which 27% had exclusively increased nonacid reflux. Cystic fibrosis patients had the highest prevalence of GOR. Pepsin was found in BALF of all patients and bile acids in BALF of 50% of the patients. Patients with BOS had neither increased GOR nor elevated pepsin in BALF. However, 70% of the patients with BOS had bile in BALF compared with 31% of stable patients. Proton pump inhibitor (PPI) treatment reduced acid reflux but did not affect nonacid reflux. Moreover, pepsin and bile levels in BALF were not reduced by PPI. One-half of the lung transplant patients had increased reflux, and nonacid reflux was common. Gastric aspiration occurred in most lung transplant patients. Pepsin was a more general marker and bile acids a more specific marker that might be associated with bronchiolitis obliterans syndrome. Proton pump inhibitor treatment did not prevent nonacid reflux and gastric aspiration.
Antidepressant Medicine Use and Risk of Developing Diabetes During the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study
Authors: Richard R. Rubin, Yong Ma, Mark Peyrot, David G. Marrero, David W. Price, Elizabeth Barrett-Connor, William C. Knowler
Journal: Diabetes Care (2010)

OBJECTIVE To assess the association between antidepressant medicine use and risk of developing diabetes during the Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS). RESEARCH DESIGN AND METHODS DPP/DPPOS participants were assessed for diabetes every 6 months and for antidepressant use every 3 months in DPP and every 6 months in DPPOS for a median 10.0-year follow-up. RESULTS Controlled for factors associated with diabetes risk, continuous antidepressant use compared with no use was associated with diabetes risk in the placebo (adjusted hazard ratio 2.34 [95% CI 1.32–4.15]) and lifestyle (2.48 [1.45–4.22]) arms, but not in the metformin arm (0.55 [0.25–1.19]). CONCLUSIONS Continuous antidepressant use was significantly associated with diabetes risk in the placebo and lifestyle arms. Measured confounders and mediators did not account for this association, which could represent a drug effect or reflect differences not assessed in this study between antidepressant users and nonusers.
Influence of Tumor Cell and Stroma Sensitivity on Tumor Response to Radiation
Authors: Kazuhiko Ogawa, Yves Boucher, Satoshi Kashiwagi, Dai Fukumura, David Chen, Leo E. Gerweck
Journal: Cancer Research (2007)

Abstract In this study, we evaluated the role of tumor cell and tumor stroma sensitivity as determinants of radiation-induced tumor growth delay. A DNA double-strand break repair–defective DNA-PKcs−/− tumor cell line and its radioresistant DNA-PKcs+/+–transfected counterpart were used to initiate tumors in nude and hypersensitive severe combined immunodeficient (SCID) mice. Insertion of the human DNA-PKcs+/+ gene substantially increased the intrinsic radioresistance of the DNA-PKcs−/− tumor cells and substantially decreased tumor response to radiation in both nude and hypersensitive SCID mice. Tumor cell radiosensitivity was the major determinant of tumor response in nude mice. In SCID mice, both tumor cell sensitivity and radiation-induced stromal damage contributed to response. The relative contribution of host and tumor cell sensitivity on tumor response was unchanged for single doses of 1 × 15 and 6 × 3 Gy–fractionated dose irradiation. [Cancer Res 2007;67(9):4015–21]
Abstract 3400: Regeneration of Human Infarcted Heart Muscle in Chronic Coronary Artery Disease after myocardial infarction: Controlled study with Intracoronary Autologous Mononuclear Bone Marrow Cell Transplantation (IACT-Study)
Authors: Matthias Koestering, Tobias Zeus, Michael Brehm, Thomas Bartsch, Christina M Schannwell, Bodo E Strauer
Journal: Circulation (2007)

Introduction: Remodeling of the left ventricle (LV) after myocardial infarction (MI) represents a major cause of infarct-related heart failure and death. After acute myocardial infarction transplantation of bone marrow cells (BMCs) leads to regeneration of infarcted zones due to neovascularization and regeneration of myocardium. We investigated cardiac performance of intracoronary transplantation of autologous BMCs in patients with chronic ischemic heart disease, suffered from transmural myocardial infarction. Methods: We treated 120 consecutive patients (51±14 years) with chronic myocardial infarction by intracoronary transplantation of autologous bone marrow mononuclear cells (BMCs) and compared them with a consecutive enrolled representative control group (n=45, 53±11 years). Bone marrow was harvested from the hip (~80 ml) and mononuclear cells were identified including CD34+, AC133+ and CD 34−, CD45−, CD14− cells. The median number of mononuclear cells harvested after overnight culture was 104 x 10 6 Results: After 3 months in the transplantation group, infarct size was reduced from (32±9 to 25±9%) significantly (p&lt;0.001), and global left ventricular ejection fraction (45±9 to 51±10%) significantly (p&lt;0.001); as well as infarction wall movement velocity (1.86 ± 0.72 to 3,12 ± 0.78cm/s) significantly (p&lt;0.001), while in the control group no significant changes were observed during 3 months follow-up in infarct size (29±9 to 28±9%), in left ventricular ejection fraction (48±10 to 50±15%) and in wall movement velocity of infarcted area (1.81 ± 0.76 to 1.92 ± 0.78cm/s). After bone marrow cell transplantation, there was an significantly (p&lt;0.05) improvement of maximum oxygen uptake (VO2max, +12%) and significantly (p&lt;0.05) of regional 18F-Fluor-Desoxy-Glucose (FDG) uptake (PET) into infarcted tissue (+15%). Conclusions: These results demonstrate that selective intracoronary transplantation of autologous BMCs may reduce infarct size and improve LV function and myocardial glucose uptake in chronic ischemic heart disease after chronic infarcted myocardium.
Malignant Transformation of<i>Hymenolepis nana</i>in a Human Host
Authors: Atis Muehlenbachs, Julu Bhatnagar, Carlos A. Agudelo, Alicia Hidron, Mark L. Eberhard, Blaine A. Mathison, Michael A. Frace, Akira Ito, Maureen G. Metcalfe, Dominique C. Rollin, Govinda S. Visvesvara, Cau D. Pham, Tara L. Jones, Patricia W. Greer, Alejandro Vélez Hoyos, Peter D. Olson, Lucy R. Diazgranados, Sherif R. Zaki
Journal: New England Journal of Medicine (2015)

Neoplasms occur naturally in invertebrates but are not known to develop in tapeworms. We observed nests of monomorphic, undifferentiated cells in samples from lymph-node and lung biopsies in a man infected with the human immunodeficiency virus (HIV). The morphologic features and invasive behavior of the cells were characteristic of cancer, but their small size suggested a nonhuman origin. A polymerase-chain-reaction (PCR) assay targeting eukaryotes identified Hymenolepis nana DNA. Although the cells were unrecognizable as tapeworm tissue, immunohistochemical staining and probe hybridization labeled the cells in situ. Comparative deep sequencing identified H. nana structural genomic variants that are compatible with mutations described in cancer. Invasion of human tissue by abnormal, proliferating, genetically altered tapeworm cells is a novel disease mechanism that links infection and cancer.
Identification of <i>Pbx1</i>, a Potential Oncogene, as a Notch3 Target Gene in Ovarian Cancer
Authors: Joon T. Park, Ie-Ming Shih, Tian-Li Wang
Journal: Cancer Research (2008)

Abstract Notch3 gene amplification has recently been identified in ovarian cancer but the Notch3 effectors that are involved in the development of ovarian cancer remain elusive. In this study, we have identified Pbx1, a proto-oncogene in hematopoietic malignancy, as a Notch3 target gene. Pbx1 expression is transcriptionally regulated by Notch3 activation, and Notch3/CSL protein complex directly binds to the Pbx1 promoter segment harboring the CSL-binding sequence. The growth-inhibitory effect of γ-secretase inhibitor could be partially reversed by ectopic Pbx1 expression. Furthermore, functional studies by Pbx1 short hairpin RNA knockdown show that Pbx1 is essential for cell proliferation and tumorigenicity. Taken together, the above findings indicate that Pbx1 is a direct Notch3-regulated gene that mediates the survival signal of Notch3 in ovarian cancer. [Cancer Res 2008;68(21):8852–60]
Cancellation of Electrocardiographic Effects During Ventricular Excitation
Authors: J. A. Abildskov, Robert M. Klein
Journal: Circulation Research (1962)

Theoretical and experimental estimates of the amount of cancellation of electrocardiographic effects of ventricular excitation have been carried out. The theoretical estimate was based on the excitation sequence reported by Scher and consisted of comparing the total length of excitation fronts at several moments in the activation process with a measurement of the uncanceled portions of these fronts. Experimental estimates in 10 dogs were based on the relative areas of spatial magnitude curves during normal ventricular excitation and during stimulation of the ventricular site yielding the largest magnitude curve area. A theoretical estimate of the cancellation to be expected during ventricular stimulation was also carried out. The theoretical estimate of cancellation of electrocardiographic effects during normal ventricular activation was 71 per cent, while the experimental estimates varied from 51 per cent to 80 per cent, with an average of 66 per cent.
Rhythmic Ryanodine Receptor Ca <sup>2+</sup> Releases During Diastolic Depolarization of Sinoatrial Pacemaker Cells Do Not Require Membrane Depolarization
Authors: Tatiana M. Vinogradova, Ying-Ying Zhou, Victor Maltsev, Alexey Lyashkov, Michael Stern, Edward G. Lakatta
Journal: Circulation Research (2004)

Localized, subsarcolemmal Ca 2+ release (LCR) via ryanodine receptors (RyRs) during diastolic depolarization of sinoatrial nodal cells augments the terminal depolarization rate. We determined whether LCRs in rabbit sinoatrial nodal cells require the concurrent membrane depolarization, or are intrinsically rhythmic, and whether rhythmicity is linked to the spontaneous cycle length. Confocal linescan images revealed persistent LCRs both in saponin-permeabilized cells and in spontaneously beating cells acutely voltage-clamped at the maximum diastolic potential. During the initial stage of voltage clamp, the LCR spatiotemporal characteristics did not differ from those in spontaneously beating cells, or in permeabilized cells bathed in 150 nmol/L Ca 2+ . The period of persistent rhythmic LCRs during voltage clamp was slightly less than the spontaneous cycle length before voltage clamp. In spontaneously beating cells, in both transient and steady states, LCR period was highly correlated with the spontaneous cycle length; and regardless of the cycle length, LCRs occurred predominantly at a constant time, ie, 80% to 90% of the cycle length. Numerical model simulations incorporating LCRs reproduce the experimental results. We conclude that diastolic LCRs reflect rhythmic intracellular Ca 2+ cycling that does not require the concomitant membrane depolarization, and that LCR periodicity is closely linked to the spontaneous cycle length. Thus, the biological clock of sinoatrial nodal pacemaker cells, like that of many other rhythmic functions occurring throughout nature, involves an intracellular Ca 2+ rhythm.
Corneal Sensitivity Is Reduced and Relates to the Severity of Neuropathy in Patients With Diabetes
Authors: Mitra Tavakoli, Panagiotis A. Kallinikos, Nathan Efron, Andrew J.M. Boulton, Rayaz A. Malik
Journal: Diabetes Care (2007)

The focus in relation to the consequences of nerve damage in diabetes has been the loss of sensation in the feet predisposing to the development of foot ulceration and lower extremity amputation (1). However, the cornea is 300–600 times more sensitive than skin (2). In addition to serving a protective function, corneal nerves regulate corneal epithelial integrity, proliferation, and wound healing (3). In diabetic patients, corneal sensitivity is reduced (4), due to a loss of corneal nerve fibers (5), which leads to corneal keratopathy (6,7) and a susceptibility to injury, with recurrent erosions and ulcers (8). Thus, these changes are analogous to the diabetic foot, but because the cornea is not exposed to high pressures, ulceration infrequently occurs. Corneal sensation is mediated via myelinated A-δ and C-nerve fibers (9,10), which can be evaluated using the Cochet-Bonnet aesthesiometer (C-BA) (2) or the noncontact corneal aesthesiometer (NCCA) (11), respectively. In diabetic patients, the C-BA has been used to show a reduction in corneal sensitivity in some (12) but not other (13) studies. Furthermore, loss of corneal sensation has been related to the severity of retinopathy (12) and neuropathy (14).

We have assessed corneal sensitivity in a large group of diabetic patients using both C-BA and NCCA to assess concordance between the two methods and also to define whether C-nerve fibers are the earliest to undergo damage (15). Using corneal confocal microscopy, we …