tbuckley/cabot-search huggingface dataset:
Changing perceptions in osteoporosis Commentary: Bone density can be used to assess fracture risk
Authors: T. J Wilkin, R. Eastell
Journal: BMJ (1999)

The purpose of this study was to define a method to assess skeletal tumor burden with <sup>18</sup>F-labeled sodium fluoride PET/CT (<sup>18</sup>F-fluoride PET/CT) and evaluate the reproducibility of these measurements. <b>Methods:</b> Ninety-eight consecutive patients (90 men; mean age ± SD, 65.7 ± 14.2 y) underwent 158 <sup>18</sup>F-fluoride PET/CT scans for evaluation of skeletal metastatic disease. In order to determine the mean normal bone SUV, initially a 1-cm spheric volume of interest (VOI) was placed over 5 bone sites: T12, L5, sacrum, right iliac bone, and right femur. For each patient, the mean SUV<sub>max</sub> for all sites was generated. Afterward, a threshold value of normal bone uptake was established. Subsequently, skeletal tumor burden was determined by generating volumetric data using a whole-body segmentation method. Any SUV<sub>max</sub> below the normal threshold was excluded from analysis, as were VOIs not related to metastatic disease. Statistics for the remaining VOIs were then generated and defined as the skeletal metastatic tumor burden by 2 parameters: total lesion fluoride uptake above an SUV<sub>max</sub> of 10 (TLF<sub>10</sub>) and fluoride tumor volume above an SUV<sub>max</sub> of 10 (FTV<sub>10</sub>). TLF<sub>10</sub> and FTV<sub>10</sub> reproducibility was determined using 2 independent and experienced PET/CT interpreters analyzing a subset of 13 <sup>18</sup>F-fluoride PET/CT scans. <b>Results:</b> Mean (±SD) normal bone SUV<sub>max</sub> was 6.62 ± 1.55 for T12, 6.11 ± 1.73 for L5, 4.59 ± 1.74 for sacrum, 5.39 ± 1.72 for right iliac bone, and 3.90 ± 1.57 for right femur. The mean normal SUV<sub>max</sub> for all 543 sites was 5.32 ± 0.99. On the basis of these values, an SUV<sub>max</sub> threshold of 10 was chosen to exclude normal bone from the volumetric calculations. Semiautomated measurements of TLF<sub>10</sub> and FTV<sub>10</sub> exhibited high interobserver reproducibility, within ±0.77% and ±3.62% of the interinterpreter average for TLF<sub>10</sub> and FTV<sub>10</sub>, respectively. <b>Conclusion:</b> Determination of skeletal tumor burden with <sup>18</sup>F-fluoride PET/CT is feasible and highly reproducible. Using an SUV<sub>max</sub> threshold of 10 excludes nearly all normal bone activity from volumetric calculations.
Extensive Human DNA Contamination in Extracts from Ancient Dog Bones and Teeth
Authors: Helena Malmström, Jan Storå, Love Dalén, Gunilla Holmlund, Anders Götherström
Journal: Molecular Biology and Evolution (2005)

Ancient DNA (aDNA) sequences, especially those of human origin, are notoriously difficult to analyze due to molecular damage and exogenous DNA contamination. Relatively few systematic studies have focused on this problem. Here we investigate the extent and origin of human DNA contamination in the most frequently used sources for aDNA studies, that is, bones and teeth from museum collections. To distinguish contaminant DNA from authentic DNA we extracted DNA from dog (Canis familiaris) specimens. We monitored the presence of a 148-bp human-specific and a 152-bp dog-specific mitochondrial DNA (mtDNA) fragment in DNA extracts as well as in negative controls. The total number of human and dog template molecules were quantified using real-time polymerase chain reaction (PCR), and the sequences were characterized by amplicon cloning and sequencing. Although standard precautions to avoid contamination were taken, we found that all samples from the 29 dog specimens contained human DNA, often at levels exceeding the amount of authentic ancient dog DNA. The level of contaminating human DNA was also significantly higher in the dog extracts than in the negative controls, and an experimental setup indicated that this was not caused by the carrier effect. This suggests that the contaminating human DNA mainly originated from the dog bones rather than from laboratory procedures. When cloned, fragments within a contaminated PCR product generally displayed several different sequences, although one haplotype was often found in majority. This leads us to believe that recognized criteria for authenticating aDNA cannot separate contamination from ancient human DNA the way they are presently used.
Increased recurrence of tuberculosis in HIV-1-infected patients in Kenya
Authors: M Hawken, P Nunn, P Godfrey-Faussett, K.P.W.J McAdam, J Morris, J Odhiambo, W Githui, C Gilks, M Hawken, S Gathua, P Nunn, M Hawken, R Brindle, B Batchelor
Journal: The Lancet (1993)
Longitudinal shape irregularity of airway lumen assessed by CT in patients with bronchial asthma and COPD
Authors: Tsuyoshi Oguma, Toyohiro Hirai, Motonari Fukui, Naoya Tanabe, Satoshi Marumo, Hajime Nakamura, Hisao Ito, Susumu Sato, Akio Niimi, Isao Ito, Hisako Matsumoto, Shigeo Muro, Michiaki Mishima
Journal: Thorax (2015)

Background Airway remodelling in bronchial asthma (BA) and COPD has been quantitatively assessed by analysing the airway wall area and the luminal area on cross-sectional CT images. To date, there have been no reports on assessment of the longitudinal structure of the airway lumen. Methods Quantitative airway analysis using CT was performed on three groups consisting of 29 patients with BA, 58 patients with COPD and 59 healthy controls. To assess the longitudinal shape irregularity of the airway lumen, new quantitative CT parameters, validated by a phantom study, were established. The internal radii of imaginary inscribed spheres in the airway lumen were measured as a function of distance from the level of the carina to the fifth-order branches of the right posterior basal bronchus. The gaps of these radii from the regression line were calculated as parameters to reflect the longitudinal airway lumen shape irregularity. These new parameters were compared among the study groups as well as with the conventional parameters of airway wall thickening and luminal area. Results Longitudinal airway lumen shape irregularity was significantly greater in patients with COPD than in those with BA and healthy controls. Wall thickening was significantly greater, and luminal area smaller, in patients with BA than in those with COPD and healthy controls. These results were consistent even among the BA and COPD subgroups with similar airflow limitation. Conclusions The combination of cross-sectional and longitudinal airway structure analyses using CT images may suggest differences in the characteristics of airway remodelling between COPD and asthma.
Threats to Validity of Nonrandomized Studies of Postdiagnosis Exposures on Cancer Recurrence and Survival
Authors: Jessica Chubak, Denise M. Boudreau, Heidi S. Wirtz, Barbara McKnight, Noel S. Weiss
Journal: JNCI Journal of the National Cancer Institute (2013)

Studies of the effects of exposures after cancer diagnosis on cancer recurrence and survival can provide important information to the growing group of cancer survivors. Observational studies that address this issue generally fall into one of two categories: 1) those using health plan automated data that contain "continuous" information on exposures, such as studies that use pharmacy records; and 2) survey or interview studies that collect information directly from patients once or periodically postdiagnosis. Reverse causation, confounding, selection bias, and information bias are common in observational studies of cancer outcomes in relation to exposures after cancer diagnosis. We describe these biases, focusing on sources of bias specific to these types of studies, and we discuss approaches for reducing them. Attention to known challenges in epidemiologic research is critical for the validity of studies of postdiagnosis exposures and cancer outcomes.
Circulating Humoral Factors and Endothelial Progenitor Cells in Patients With Differing Coronary Collateral Support
Authors: Pier D. Lambiase, Richard J. Edwards, Prodromos Anthopoulos, Salman Rahman, Y. Gloria Meng, Clifford A. Bucknall, Simon R. Redwood, Jeremy D. Pearson, Michael S. Marber
Journal: Circulation (2004)

The mechanisms underlying the variation in collateral formation between patients, even with similar patterns of coronary artery disease, remain unclear. This study investigates whether circulating humoral or cellular factors can provide an insight into this variation.Thirty patients with isolated left anterior descending coronary artery disease underwent percutaneous coronary intervention with collateral flow index (CFI) determined using a pressure wire. Patients with inadequate (CFI <0.25) compared with those with adequate (CFI > or =0.25) collateral support had, or tended to have, lower concentrations of coronary sinus growth factors and plasma exerting a weaker effect on endothelial cell migration and angiogenesis in vitro. However, there was an inverse correlation between serum mitogenicity and CFI (r=-0.61, P<0.01). No significant differences were detected between the 2 groups in plasma levels of total vascular endothelial growth factor, vascular endothelial growth factor165, or placental growth factor. There was a strong positive correlation between numbers of CD34/CD133-positive circulating hemopoietic precursor cells and CFI (r=0.75, P<0.001). In patients with inadequate, compared with those with adequate, CFI, the numbers of differentiated endothelial progenitor cells (EPCs) appearing in the circulation and in culture were significantly reduced by 75% (P<0.05) and 70% (P<0.05), respectively.In this study, inadequate coronary collateral development is associated with reduced numbers of circulating EPCs and impaired chemotactic and proangiogenic but not mitogenic activity. These findings are consistent with current efforts to enhance collateral formation by augmentation of circulating EPCs.
Lipopolysaccharide induces cholangiocyte proliferation via an interleukin-6-mediated activation of p44/p42 mitogen-activated protein kinase
Authors: Joongwon Park, Gregory J. Gores, Tushar Patel
Journal: Hepatology (1999)

The biliary epithelium is exposed to mediators of inflammation such as bacterial endotoxin or lipopolysaccharide (LPS) in a variety of inflammatory conditions. These conditions are also characterized by cholangiocyte proliferation and a predisposition to malignancy. Furthermore, LPS can enhance the expression of interleukin–6 (IL–6), a known biliary mitogen. However, the effects of LPS on cholangiocyte proliferation or IL–6 secretion are unknown. Thus, our aims were to determine if LPS stimulates cholangiocyte proliferation by IL–6-dependent signaling pathways. H69 cells derived from normal human intrahepatic cholangiocytes proliferated in response to LPS. Cholangiocytes responded to LPS (and other inflammatory cytokines such as tumor necrosis factor α [TNF–α] and IL–1β) by increased secretion of IL–6, which had a mitogenic effect on H69 cells. Preincubation with anti-IL–6 neutralizing antibodies inhibited LPS–induced proliferation. Furthermore, cholangiocytes possessed the IL–6 receptor complex subunits and intact signaling mechanisms leading to activation of signal transducers and activators of transcription (STAT) factors. Although both p38 and p44/p42 mitogen–activated protein kinases (MAPKs) were constitutively present and active in cholangiocytes, IL–6 increased p44/p42, but not p38 MAPK activity. PD098059 inhibited activation of p44/p42 MAPK in cholangiocytes and completely blocked DNA synthesis in response to IL–6 or LPS. These studies identify a critical role for the p44/p42 MAPK in cholangiocyte proliferation and demonstrate that the proliferative response of cholangiocytes to inflammatory mediators such as LPS involves IL–6-mediated activation of the p44/p42 MAPK pathway
Estrogen Actions in the Central Nervous System<sup>1</sup>
Authors: Bruce S. McEwen, Stephen E. Alves
Journal: Endocrine Reviews (1999)

I. Introduction II. Mechanisms of Estrogen Action A. “Genomic” and “nongenomic” mechanisms B. Steroid hormone actions on gene expression C. Subtypes of estrogen receptors D. Steroid hormone actions on putative receptors on membranes E. Rapid actions of steroids on neuronal excitability F. Steroid hormone actions via second messengers G. Neuroprotective effects of estrogens H. Summary III. Areas of the Brain Affected Outside of the Hypothalamus A. Studies of hypothalamic and extrahypothalamic actions of estrogens B. Estrogens and the cholinergic system C. Estrogens and the serotonergic system D. Catecholaminergic neurons E. Spinal cord F. Hippocampus G. Glial cells, endothelial cells, and the blood-brain barrier H. Summary IV. Effects of Estrogens on Learning and Memory V. Estrogens, Neuroprotection, and Alzheimer’s Disease VI. Conclusions
P47 Post-Operative Oxygen Saturation, Prescribing &amp; Administration in Patients Undergoing Elective Orthopaedic Surgery
Authors: AM Hogan, E Anand, MJ Oddy, J Welch, H Booth
Journal: Thorax (2012)

<h3>Introduction</h3> There is increasing interest in maximising perioperative care of surgical patients, including response to oxygen desaturation which may occur in association with anaesthesia, analgesic/sedative drugs, and/or indicate pathology. There is thus potentially great importance in understanding the incidence and profile of oxygen desaturation in the post-operative patient, and documenting our response to it. <h3>Methods</h3> We recorded sequential SpO2 values and oxygen prescription/administration from the charts of 65 patients (mean age 56.5 years (<i>SD</i> 20.2), BMI 29.6 (10.5), 38 Females) admitted to University College London Hospital for elective orthopaedic surgery, starting at point of transfer from recovery room to ward. Nine were current smokers, one patient had COPD, and eight had possible sleep apnoea. None used home oxygen or CPAP and all were normoxic pre-operatively. <h3>Results</h3> One-third (30.8%; 20/65) of patients experienced an isolated, minor desaturation event (Figure 1): mean minimum SpO<sub>2</sub> 91.9% (<i>SD</i> 2.2). ‘Desaturators’ were older (<i>P</i>=0.038) but not ‘sicker’ compared to those who remained normoxic, determined by smoking status and ASA grade, and by post-operative rate of chest x-ray request, blood transfusion, and antibiotic requirement. Thus, the majority of desaturations were minor and of limited clinical significance; in a few cases perhaps representing spurious values. Recurrent (&gt;/= 3 desaturations/24 hours) with/without more serious desaturations (&lt;90% SpO<sub>2</sub>) occurred in 6.2% (4/65). Oxygen was prescribed for only one-third of patients (35.4%; 23/65), but was administered to three-quarters (75.4%; 49/65) typically as a gradual ‘down-titration’ of high-flows given in recovery rather than in response to desaturation. Some patients remained on oxygen despite sequential SpO<sub>2</sub> values of 100%. Strong opiates were frequently prescribed (93.8%; 61/65), sometimes with night sedation (9.2%; 6.65). <h3>Comment</h3> British Thoracic Society national guidelines encourage oxygen administration titrated to SpO<sub>2</sub>, but we show that this aim may not currently be fully realized in surgical patients, perhaps partly due to lack of routine oxygen prescribing. Encouragement of early oxygen prescribing by surgeons and anaethetists, who already routinely prescribe thrombo-prophylaxis, prophylactic antibiotics and analgesia, might help to ensure that patients are set-up for better matching of oxygen administration to need for the duration of their post-operative recovery.
The Long-Term Effects of Self-Management Education for Patients With Type 2 Diabetes on Glycemic Control
Authors: Hirohito Sone, Hideki Ito, Yasushi Saito, Hidetoshi Yamashita, Shun Ishibashi, Shigehiro Katayama, Ryuzo Abe, Yasuo Ohashi, Yasuo Akanuma, Nobuhiro Yamada
Journal: Diabetes Care (2002)

Comment -I interpret these results to support the recommendation of both the American Kidney Foundation and the American Diabetes Association that ACR can be used instead of a timed collection.Timed collections, 24 h or otherwise, are very inconvenient and often not collected accurately.Since albumin excretion is highly variable from day to day (up to 25%), a repeat ACR to fulfill the criterion of two of three positive values within a 3-to 6-month period as recommended for the diagnosis of microalbuminuria would very likely have reduced the false-positive rate of 6%.Mogensen CE: Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes.
Adipocytes Impair Leukemia Treatment in Mice
Authors: James W. Behan, Jason P. Yun, Marina P. Proektor, Ehsan A. Ehsanipour, Anna Arutyunyan, Ara S. Moses, Vassilios I. Avramis, Stan G. Louie, Anna Butturini, Nora Heisterkamp, Steven D. Mittelman
Journal: Cancer Research (2009)

Abstract Obesity is associated with increased cancer incidence and mortality. We have previously found that obesity in children is associated with a 50% increased recurrence of acute lymphoblastic leukemia (ALL) in high-risk patients. We have therefore developed novel in vivo and in vitro preclinical models to study the mechanism(s) of this association. Obesity increased relapse after monotherapy with vincristine (P = 0.03) in obese mice injected with syngeneic ALL cells. This occurred although the drug was dosed proportionally to body weight, equalizing blood and tissue drug levels. In coculture, 3T3-L1 adipocytes significantly impaired the antileukemia efficacy of vincristine, as well as three other chemotherapies (P &amp;lt; 0.05). Interestingly, this protection was independent of cell-cell contact, and it extended to human leukemia cell lines as well. Adipocytes prevented chemotherapy-induced apoptosis, and this was associated with increased expression of the two prosurvival signals Bcl-2 and Pim-2. These findings highlight the role of the adipocyte in fostering leukemia chemotherapy resistance, and may help explain the increased leukemia relapse rate in obese children and adults. Given the growing prevalence of obesity worldwide, these effects are likely to have increasing importance to cancer treatment. [Cancer Res 2009;69(19):7867–74]
Age at Onset in Bipolar I Affective Disorder: Further Evidence for Three Subgroups
Authors: Frank Bellivier, Jean-Louis Golmard, Marcella Rietschel, Thomas G. Schulze, Alain Malafosse, Martin Preisig, Patrick McKeon, Lesley Mynett-Johnson, Chantal Henry, Marion Leboyer
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Preliminary data suggested that there are three subgroups of bipolar affective disorder based on age at onset. The authors sought to replicate those findings and determine the cut-off age of each subgroup. METHOD: Admixture analysis was used to determine the best-fitting model for the observed ages at onset of 368 consecutively admitted patients. The results obtained were compared with those of the previously described model. The authors also investigated whether affected siblings are more likely to belong to the same theoretical age-at-onset subgroup as identified by admixture analysis. RESULTS: The existence of three subgroups defined by age at onset was confirmed. The mean ages estimated in this model were 17.4 years (SD=2.3), 25.1 years (SD=6.2), and 40.4 years (SD=11.3). Affected siblings were more likely to belong to the same theoretical subgroup. CONCLUSIONS: There are three age-at-onset subgroups of bipolar patients, and specific familial vulnerability factors might underlie each subgroup.
Genomic data sharing for translational research and diagnostics
Authors: Peter N Robinson
Journal: Genome Medicine (2014)

Translational genomics is changing, not only in the technology used but also in the sharing of data. The enormous potential for genomics technologies to improve patient care has been recognized, but it will not be reached unless powerful but secure data-sharing technologies are developed. A recent study demonstrates the power of federated queries, in which sequence variants can be searched simultaneously in files distributed over multiple centers.
Identification of New Compounds That Trigger Apoptosome-Independent Caspase Activation and Apoptosis
Authors: Emanuela Aleo, Clare J. Henderson, Alessandra Fontanini, Barbara Solazzo, Claudio Brancolini
Journal: Cancer Research (2006)

Abstract Identification of alternative pathways of caspase activation is an important step to develop new antitumor treatments. We report here the result of a screening with a small chemical library, the Developmental Therapeutics Program-National Cancer Institute “challenge set,” on cells expressing mutated caspase-9. We have identified two molecules capable of activating an apoptosome-independent apoptotic pathway. These compounds, named F6 and G5, target the ubiquitin-proteasome system by inhibiting the ubiquitin isopeptidases. We have shown that F6 and G5 induce a rather unique apoptotic pathway, which includes a Bcl-2-dependent but apoptosome-independent mitochondrial pathway with up-regulation of the BH3-only protein Noxa, stabilization of the inhibitor of apoptosis antagonist Smac, but also the involvement of the death receptor pathway. Noxa plays an important role in the induction of mitochondrial fragmentation and caspase activation, whereas the death receptor pathway becomes critical in the absence of a functional apoptosome. This study suggests that screening of chemical libraries on cancer cells with defined mutations in apoptotic key elements can lead to the identification of compounds that are useful to characterize alternative pathways of caspase activation. (Cancer Res 2006; 66(18): 9235-44)
A Microchip CD4 Counting Method for HIV Monitoring in Resource-Poor Settings
Authors: William R Rodriguez, Nicolaos Christodoulides, Pierre N Floriano, Susan Graham, Sanghamitra Mohanty, Meredith Dixon, Mina Hsiang, Trevor Peter, Shabnam Zavahir, Ibou Thior, Dwight Romanovicz, Bruce Bernard, Adrian P Goodey, Bruce D Walker, John T McDevitt
Journal: PLoS Medicine (2005)

More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed.Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity.Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality.