tbuckley/cabot-search huggingface dataset:
A cluster of lung injury cases associated with home humidifier use: an epidemiological investigation
Authors: Hwa Jung Kim, Moo-Song Lee, Sang-Bum Hong, Jin Won Huh, Kyung-Hyun Do, Se Jin Jang, Chae-Man Lim, Eun Jin Chae, Hanyi Lee, Miran Jung, Young-Joon Park, Ji-Hyuk Park, Geun-Yong Kwon, Jin Gwack, Seung-Ki Youn, Jun-Wook Kwon, Byung-Guk Yang, Byung-Yool Jun, Yangho Kim, Hae-Kwan Cheong, Byung Chul Chun, Heon Kim, Kyuhong Lee, Younsuck Koh
Journal: Thorax (2014)

<h3>Background</h3> In April 2011 a tertiary hospital in Seoul, Korea reported several cases of severe respiratory distress of unknown origin in young adults. <h3>Methods</h3> To find the route of transmission, causative agent and patient risk factors of the outbreak, an investigation of the epidemic was initiated. Clinicopathological conferences led to the suspicion that the cases related to an inhalation injury. An age- and sex-matched case–control study was therefore performed to examine the inhalation exposure of the patients to various agents. <h3>Results</h3> Of the 28 confirmed cases, 18 agreed to participate. A total of 121 age- and sex-matched controls with pulmonary, allergic or obstetric disease were selected. All patients and controls completed questionnaires with questions about exposure to various inhalants. The crude ORs for patient exposure to indoor mould, humidifier use, humidifier detergent use and insecticide use were 4.4 (95% CI 1.5 to 13.1), 13.7 (95% CI 1.8 to 106.3), 47.3 (95% CI 6.1 to 369.7) and 3.9 (95% CI 1.3 to 11.7), respectively. However, when considered concurrently, indoor mould and insecticide use lost statistical significance. Moreover, humidifier use was ruled out as the cause because of a lack of biological plausibility and the weak strength of the association. This suggested that humidifier disinfectant was the cause of the outbreak. This information led the Korean government to order the removal of humidifier detergents from the market. In the years following the ban, no additional cases were detected. <h3>Conclusions</h3> Epidemiological evidence strongly suggests that the lung injury outbreak was caused by humidifier detergent use at home.
The Caucasus as an Asymmetric Semipermeable Barrier to Ancient Human Migrations
Authors: B. Yunusbayev, M. Metspalu, M. Jarve, I. Kutuev, S. Rootsi, E. Metspalu, D. M. Behar, K. Varendi, H. Sahakyan, R. Khusainova, L. Yepiskoposyan, E. K. Khusnutdinova, P. A. Underhill, T. Kivisild, R. Villems
Journal: Molecular Biology and Evolution (2011)

The Caucasus, inhabited by modern humans since the Early Upper Paleolithic and known for its linguistic diversity, is considered to be important for understanding human dispersals and genetic diversity in Eurasia. We report a synthesis of autosomal, Y chromosome, and mitochondrial DNA (mtDNA) variation in populations from all major subregions and linguistic phyla of the area. Autosomal genome variation in the Caucasus reveals significant genetic uniformity among its ethnically and linguistically diverse populations and is consistent with predominantly Near/Middle Eastern origin of the Caucasians, with minor external impacts. In contrast to autosomal and mtDNA variation, signals of regional Y chromosome founder effects distinguish the eastern from western North Caucasians. Genetic discontinuity between the North Caucasus and the East European Plain contrasts with continuity through Anatolia and the Balkans, suggesting major routes of ancient gene flows and admixture.
Design and Endpoints of Clinical Trials in Hepatocellular Carcinoma
Authors: Josep M. Llovet, Adrian M. Di Bisceglie, Jordi Bruix, Barnett S. Kramer, Riccardo Lencioni, Andrew X. Zhu, Morris Sherman, Myron Schwartz, Michael Lotze, Jayant Talwalkar, Gregory J. Gores
Journal: JNCI Journal of the National Cancer Institute (2008)

The design of clinical trials in hepatocellular carcinoma (HCC) is complex because many patients have concurrent liver disease, which can confound the assessment of clinical benefit. There is an urgent need for high-quality trials in this disease. An expert panel was convened by the American Association for the Study of Liver Diseases to develop guidelines that provide a common framework for designing trials to facilitate comparability of results. According to these guidelines, randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC. Survival remains the main endpoint to measure effectiveness in phase 3 studies, whereas time to recurrence is proposed as an appropriate endpoint in the adjuvant setting. Because progression-free survival and disease-free survival are composite endpoints, they are more vulnerable than others in HCC clinical studies and may not be able to capture clinical benefits. Selection of the target population should be based on the Barcelona Clinic Liver Cancer staging system. New drugs should be tested in patients with well-preserved liver function (Child-Pugh A class). Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Further research is needed to incorporate biomarkers and molecular imaging into clinical research in HCC. These surrogate markers may help to enrich study populations and maximize the cost-benefit ratio of trial execution. Design and conduct of phase 3 trials should be coordinated by centers with appropriate expertise in HCC.
Multiple rib infarcts: a rare form of osteonecrosis in antiphospholipid syndrome
Authors: W-H Yoo
Journal: Annals of the Rheumatic Diseases (2004)

Osteonecrosis (ON) is a well known morbidity of several rheumatic diseases, usually affecting the hip, knee, shoulder, and ankle. The involvement of multiple or atypical sites by ON has been reported, especially in association with antiphospholipid antibodies (aPL). Rib infarction has been reported as a painful crisis of sickle cell disease, but has not been reported in rheumatic diseases. I describe here the first case of rib infarcts which developed in a patient with mixed connective tissue disease (MCTD) and secondary antiphospholipid syndrome (APS).

A 36 year old woman with hand oedema, Raynaud’s phenomenon, and polyarthritis of both hands was diagnosed as having MCTD 3 years ago. She had deep venous thromboses in both legs 2 years ago. Laboratory tests showed an antinuclear antibody titre of 1/2560, IgG anticardiolipin antibody 65.42 GPU (normal <15 GPU), and anti-U1RNP antibody (1/1280). Secondary APS associated with MCTD was diagnosed, and treatment with low dose steroid, …
Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial
Authors: Ravi A Madan, Mahsa Mohebtash, Philip M Arlen, Matteo Vergati, Myrna Rauckhorst, Seth M Steinberg, Kwong Y Tsang, Diane J Poole, Howard L Parnes, John J Wright, William L Dahut, Jeffrey Schlom, James L Gulley
Journal: The Lancet Oncology (2012)
Nodal myosin distribution in the bovine heart during prenatal development: an immunohistochemical study.
Authors: L Gorza, L E Thornell, S Schiaffino
Journal: Circulation Research (1988)

A novel type of cardiac myosin heavy chain, immunologically related to the myosin isoforms expressed during skeletal muscle development, has recently been described in sinoatrial and atrioventricular nodal fibers of the adult bovine heart (Gorza et al, J Cell Biol 1986; 102:1758-1766). The tissue-specific expression of this myosin type has been utilized in the present study to investigate the differentiation of nodal fibers during cardiac development. In 4-6-week-old bovine embryos, reactivity for nodal myosin was observed in a cluster of cardiac fibers in the sinus venosus wall, corresponding to the sinoatrial node primordium and in a number of fibers localized in the left atrial wall, especially in proximity to vascular orifices, possibly corresponding to the postulated left-sided sinoatrial node. In contrast, reactivity for nodal myosin was not detected in the atrioventricular node until 12 weeks of gestation. Before this stage, fibers reactive for nodal myosin were also seen scattered in the left atrial wall and interatrial septum, raising the possibility that atrioventricular nodal fibers may derive from the left-sided sinoatrial node. Reactivity for nodal myosin was never seen in normal atrial and ventricular myocardium, nor in the ventricular conduction tissue, indicating that nodal myosin does not represent a primordial myosin form, but is rather a specific marker of a distinct muscle cell lineage.
Ondansetron in Pregnancy and Risk of Adverse Fetal Outcomes
Authors: Björn Pasternak, Henrik Svanström, Anders Hviid
Journal: New England Journal of Medicine (2013)

Ondansetron is frequently used to treat nausea and vomiting during pregnancy, but the safety of this drug for the fetus has not been well studied.We investigated the risk of adverse fetal outcomes associated with ondansetron administered during pregnancy. From a historical cohort of 608,385 pregnancies in Denmark, women who were exposed to ondansetron and those who were not exposed were included, in a 1:4 ratio, in propensity-score-matched analyses of spontaneous abortion (1849 exposed women vs. 7396 unexposed women), stillbirth (1915 vs. 7660), any major birth defect (1233 vs. 4932), preterm delivery (1792 vs. 7168), and birth of infants at low birth weight and small for gestational age (1784 vs. 7136). In addition, estimates were adjusted for hospitalization for nausea and vomiting during pregnancy (as a proxy for severity) and the use of other antiemetics.Receipt of ondansetron was not associated with a significantly increased risk of spontaneous abortion, which occurred in 1.1% of exposed women and 3.7% of unexposed women during gestational weeks 7 to 12 (hazard ratio, 0.49; 95% confidence interval [CI], 0.27 to 0.91) and in 1.0% and 2.1%, respectively, during weeks 13 to 22 (hazard ratio, 0.60; 95% CI, 0.29 to 1.21). Ondansetron also conferred no significantly increased risk of stillbirth (0.3% for exposed women and 0.4% for unexposed women; hazard ratio, 0.42; 95% CI, 0.10 to 1.73), any major birth defect (2.9% and 2.9%, respectively; prevalence odds ratio, 1.12; 95% CI, 0.69 to 1.82), preterm delivery (6.2% and 5.2%; prevalence odds ratio, 0.90; 95% CI, 0.66 to 1.25), delivery of a low-birth-weight infant (4.1% and 3.7%; prevalence odds ratio, 0.76; 95% CI, 0.51 to 1.13), or delivery of a small-for-gestational-age infant (10.4% and 9.2%; prevalence odds ratio, 1.13; 95% CI, 0.89 to 1.44).Ondansetron taken during pregnancy was not associated with a significantly increased risk of adverse fetal outcomes. (Funded by the Danish Medical Research Council.).
Does Measurement Site for Visceral and Abdominal Subcutaneous Adipose Tissue Alter Associations With the Metabolic Syndrome?
Authors: Jennifer L. Kuk, Timothy S. Church, Steven N. Blair, Robert Ross
Journal: Diabetes Care (2006)

OBJECTIVE—To determine whether the associations between visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), and the metabolic syndrome are altered depending on measurement site for VAT and ASAT and the definition used to identify the metabolic syndrome. RESEARCH DESIGN AND METHODS—Total VAT and ASAT volume was derived using ∼37 contiguous computed tomography (CT) images from T10–T11 to L5–S1 in 85 men. CT images obtained at eight intervertebral locations (e.g., L4–L5, L3–L4, etc.) were used to determine the associations between partial volumes (single images) and metabolic syndrome. Metabolic syndrome was defined using the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. Logistic regression was used to calculate the odds ratio (OR) per SD increase in adipose tissue. RESULTS—For total and all partial volumes, VAT was more strongly associated with metabolic syndrome than ASAT independent of metabolic syndrome criteria. The OR (per SD) for NCEP metabolic syndrome was higher for total VAT volume (OR = 7.26) and for the partial volumes at T12–L1 (7.46) and L1–L2 (8.77) than those at the L4–L5 level (3.94). The OR for metabolic syndrome (∼2.6) was not substantially different among the ASAT measures. A similar pattern of association was observed using the IDF metabolic syndrome criteria. CONCLUSIONS—The measurement site for VAT, but not for ASAT, has a substantial influence on the magnitude of the association with both metabolic syndrome definitions. However, because VAT remained significantly associated with metabolic syndrome regardless of measurement site, the clinical interpretation was unaltered by measurement protocol or metabolic syndrome definition.
Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes
Authors: Pär G Engström, David Fredman, Boris Lenhard
Journal: Genome biology (2008)

Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains. We describe Ancora http://ancora.genereg.net, a web resource that provides data and tools for exploring genomic organization of HCNEs for multiple genomes. Ancora includes a genome browser that shows HCNE locations and features novel HCNE density plots as a powerful tool to discover developmental regulatory genes and distinguish their regulatory elements and domains.
Protection of total body water content and absence of hyperthermia despite 2% body mass loss (‘voluntary dehydration’) in soldiers drinking ad libitum during prolonged exercise in cool environmental conditions
Authors: Heinrich W Nolte, Timothy D Noakes, Bernard van Vuuren
Journal: British Journal of Sports Medicine (2010)

The extent to which humans need to replace fluid losses during exercise remains contentious despite years of focused research. The primary objective was to evaluate ad libitum drinking on hydration status to determine whether body mass loss can be used as an accurate surrogate for changes in total body water (TBW) during exercise. Data were collected during a 14.6-km route march (wet bulb globe temperature of 14.1°C ). 18 subjects with an average age of 26±2.5 (SD) years participated. Their mean ad libitum total fluid intake was 2.1±1.4 litres during the exercise. Predicted sweat rate was 1.289±0.530 l/h. There were no significant changes (p&gt;0.05) in TBW, urine specific gravity or urine osmolality despite an average body mass loss (p&lt;0.05) of 1.3±0.45 kg during the march. Core temperature rose as a function of marching speed and was unrelated to the % change in body mass. This suggests that changes in mass do not accurately predict changes in TBW (r=−0.16) because either the body mass loss during exercise includes losses other than water or there is an endogenous body water source that is released during exercise not requiring replacement during exercise, or both. Ad libitum water replacement between 65% and 70% of sweat losses maintained safe levels of hydration during the experiment. The finding that TBW was protected by ad libitum drinking despite ∼2% body mass loss suggests that the concept of ‘voluntary dehydration’ may require revision.
Effect of thromboxane A2 inhibitors on allergic pulmonary inflammation in mice
Authors: H Shi, A Yokoyama, N Kohno, Y Hirasawa, K Kondo, K Sakai, K Hiwada
Journal: European Respiratory Journal (1998)

Thromboxane (Tx)A2 synthase inhibitors and thromboxane prostanoid (TP) receptor antagonists have been developed as anti-asthma drugs. TxA2 may contribute to airflow limitation and bronchial hyperresponsiveness, and these compounds have been demonstrated to improve them. However, it is not known whether TxA2 is involved in bronchial inflammation. To address this question, we explored the influences of OKY-046 (a TxA2 synthase inhibitor) and S-1452 (a TP receptor antagonist) on eosinophilic inflammation of the airways using a murine model. BALB/c mice sensitized with ovalbumin and challenged by repeated exposure to ovalbumin yielded marked eosinophilia in bronchoalveolar lavage fluid (BALF). Treatment with either compound significantly reduced the number of total cells and eosinophils in BALF in a dose-dependent manner. The production of interleukin (IL)-5, IL-2 and interferon (IFN)-gamma by antigen-stimulated splenic mononuclear cells (SMNC) was significantly decreased in mice treated with either compound compared to that in untreated mice. Furthermore, both compounds inhibited proliferation and cytokine production of SMNC in vitro. These results suggest that both OKY-046 and S-1452 are capable of inhibiting production of cytokines, which in turn inhibits eosinophil infiltration into the murine airway. Thus, both thromboxane A2 synthesis inhibitors and thromboxane prostanoid antagonists may be effective as anti-inflammatory drugs in the treatment of asthma.
Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in normoglycemic but not diabetic female mice
Authors: Liqun Zhang, Aji Nair, Kyle Krady, Christopher Corpe, Robert H. Bonneau, Ian A. Simpson, Susan J. Vannucci
Journal: Journal of Clinical Investigation (2004)

Diabetic hyperglycemia increases ischemic brain damage in experimental animals and humans. The mechanisms are unclear but may involve enhanced apoptosis in penumbral regions. Estrogen is an established neuroprotectant in experimental stroke. Our previous study demonstrated that female diabetic db/db mice suffered less damage following cerebral hypoxia-ischemia (H/I) than male db/db mice. Here we investigated the effects of diabetes and estrogen apoptotic gene expression following H/I. Female db/db and nondiabetic (+/?) mice were ovariectomized (OVX) and treated with estrogen or vehicle prior to H/I; brains were analyzed for damage and bcl-2 family gene expression. OVX increased ischemic damage in +/? mice; estrogen reduced tissue injury and enhanced antiapoptotic gene expression (bcl-2 and bfl-1). db/db mice demonstrated more damage, without increased bcl-2 mRNA; bfl-1 expression appeared at 48 hours of recovery associated with infarction. To our knowledge, this is the first description of bfl-1 in the brain with localization to microglia and macrophages. Early induction of bfl-1 expression in +/? mouse brain was associated with microglia; delayed bfl-1 expression in diabetic brain was in macrophages bordering the infarct. Furthermore, estrogen replacement stimulated early postischemic expression of bcl-2 and bfl-1 and reduced damage in normoglycemic animals but failed to protect the diabetic brain.
Surgical treatment for myasthenia gravis.
Authors: T J Otto, H Strugalska
Journal: Thorax (1987)

A new surgical technique for thymectomy is presented. Three hundred and seventeen patients with myasthenia gravis and 20 with thymomas who had myasthenic symptoms were operated on. The new surgical approach--a small transverse sternotomy--was used in 257 cases (in 240 patients with myasthenia gravis and 17 with thymomas) and conventional median sternotomy in 80. In myasthenic patients small transverse sternotomy enabled radical thymectomy to be performed with an uneventful postoperative course and very good cosmetic results. There were no hospital deaths among patients with myasthenia gravis after thymectomy. The long term results, assessed after 18-24 months, were good: the total remission rate was 39.5%, and there was a great improvement in 48.5% and an improvement in 9%. After thymectomy about 30% of patients received supplementary treatment with prednisone. A correlation between the duration of symptoms and the result of thymectomy was established: the shorter the duration of myasthenia gravis the better the results. In the small group of 20 patients with thymomas two died in hospital. In 12 patients with encapsulated thymic tumours the long term results were similar to those in patients with myasthenia gravis, whereas in patients with infiltrating thymic tumours the results were unsatisfactory.
Phasic coronary blood flow velocity in intramural and epicardial coronary arteries.
Authors: W M Chilian, M L Marcus
Journal: Circulation Research (1982)

Knowledge concerning phasic coronary blood flow is based primarily on measurements obtained from epicardial coronary arteries, which, in part, function as capacitors. If present, epicardial capacitance effects could obscure the dynamic nature of phasic intramyocardial perfusion. To analyze this effect of epicardial capacitance, we simultaneously measured coronary blood flow velocity in an epicardial artery (left anterior descending) and an intramural artery (septal) in open-chest, anesthetized dogs. During control conditions, the percentage of total coronary blood flow velocity occurring during diastole per cardiac cycle was significantly greater (P less than 0.05) in the septal artery (92%) than in the left anterior descending artery (75%). Furthermore, blood flow velocity during mid-systole in the septal artery was retrograde (-7.2%), whereas blood flow velocity at this time was antegrade in the left anterior descending artery (+3.5%). Blood flow velocity measurements from small epicardial arteries just before they penetrated into the myocardium revealed a phasic pattern similar to that of the septal artery. This suggests that the phasic blood velocity pattern in penetrating coronary arteries, in general, is different than that in large epicardial arteries. During vasodilation following nitroglycerin, dipyridamole, or a 20-second occlusion of the left main coronary artery, the retrograde component of mid-systolic blood velocity persisted in the septal artery, despite large increases (300-400%) in the mid-systolic antegrade component of blood flow velocity in the left anterior descending artery. These qualitative and quantitative differences in phasic blood flow velocity between intramural and large epicardial arteries are best reconciled by postulating the existence of a significant coronary capacitor.
Distribution of postsynaptic density proteins in rat kidney: Relationship to neuronal nitric oxide synthase
Authors: A Tojo, D S Bredt, C S Wilcox
Journal: Kidney International (1999)

Distribution of postsynaptic density proteins in rat kidney: Relationship to neuronal nitric oxide synthase. <h3>Background</h3> Neuronal nitric oxide synthase (nNOS) is expressed in skeletal muscle beneath the sarcolemma associated with dystrophin complex. In brain, nNOS is anchored to synaptic membranes by specific postsynaptic density proteins (PSD)-95 and PSD-93. We have investigated the cellular and subcellular localization of these PSD proteins in the kidney and their relationship to nNOS and the cell membrane. <h3>Methods</h3> Kidneys from male Sprague-Dawley rats were processed for light and electron microscopic immunohistochemistry with polyclonal antibodies against PSD and nNOS proteins. <h3>Results</h3> Western blot analysis of rat kidney revealed a specific band for PSD-93 at the molecular weight of 103kDa. Immunostaining for PSD-93 was located in the thick ascending limb of the loop of Henle, macula densa cells, distal convoluted tubules, cortical collecting ducts, outer and inner medullary collecting duct, glomerular epithelium, and Bowman's capsule. A pre-embedding electron microscopic immunoperoxidase procedure localized PSD-93 to the basolateral membrane of these tubular cells. Using different sized immunogold particles, a portion of nNOS in the macula densa colocalized with PSD-93 adjacent to cytoplasmic vesicles and the basolateral membrane. In contrast, PSD-95 protein was detected only weakly in the cortex by Western blot. Immunostaining for PSD-95 was located only faintly in the apical membrane of the thick ascending limb, macula densa, distal convoluted tubule, and cortical collecting duct cells. <h3>Conclusion</h3> PSD-93 is the predominant PSD expressed in the rat kidney. It is located primarily in the basolateral membranes of distal nephron and colocalizes with a pool of nNOS in cytoplasmic vesicles and basolateral membranes of macula densa cells.