tbuckley/cabot-search huggingface dataset:
Incorporating the Results of Diabetes Research Into Clinical Practice
Authors: Charles M. Clark Jr., Marshall H. Chin, Stephen N. Davis, Edwin Fisher, Roland G. Hiss, David G. Marrero, Elizabeth A. Walker, Judith Wylie-Rosett
Journal: Diabetes Care (2001)

In our July issue, Dr. Roland Hiss presented the paradigm of the Michigan Diabetes Research and Training Center’s (DRTC’s) approach to the difficulties and opportunities of translating the results of clinical studies into clinical practice (1). As the DRTCs reach their 25th anniversary, it seems appropriate to review their progress in understanding and improving the translation of clinical trials into clinical practice. I have asked the coordinators of translation research of the six DRTCs to briefly summarize their approaches and successes in this area, which follow.

It is important to note that the DRTCs began in 1977 in an environment where we knew that there were huge gaps between the results of clinical trials and clinical practice, but we knew little about why those gaps existed, nor did we know how to close them. In large measure our progress in translation research and our successes in translating the subsequent landmark clinical trials into practice are and will continue to be a result of the research conducted by the DRTCs. All of the DRTCs have made vital contributions to this area of research. We present their experiences in alphabetical order.

### Marshall H. Chin, MD, MPH, Associate Professor of Medicine.

The University of Chicago’s DRTC Demonstration and Education (D&E ) cores have focused on developing provider-, patient-, and systems-level interventions to improve the quality of care and health outcomes of diabetic patients, with a concentration on particularly vulnerable minority and low-income patients. Initially, the University of Chicago aimed to train health care professionals to deliver state-of-the-art diabetes care. To help disseminate these educational programs beyond a regional level, it initiated national collaborative efforts with the American Diabetes Association and the American Association of Diabetes Educators (2,3,4). For example, the American Association of Diabetes Educators published Diabetes Update : From the Basics Forward , which was a detailed …
Bronchiectasis: an orphan disease with a poorly-understood prognosis
Authors: T Keistinen, O Saynajakangas, T Tuuponen, SL Kivela
Journal: European Respiratory Journal (1997)

The prognosis and risk factors for bronchiectasis are at present poorly known. The aim of this study was to examine the long-term prognosis and cause of death in this disease. The National Hospital Discharge Register was used to search for patients aged 35-74 yrs, with newly-diagnosed bronchiectasis in the period 1982-1986. Each of the 842 patients identified was matched with an asthmatic patient and a patient with chronic obstructive pulmonary disease (COPD), who were of the same age and sex and who had been treated in hospital at the same time. The use of hospital services by these subjects was examined up to the end of 1992, and mortality to the end of 1993. The prognosis for the bronchiectatic patients treated in hospital was better than that for the COPD patients but poorer than that for the asthmatics; the risk of death being 1.25 (95% confidence interval (95% CI) 1.15-1.36) for the COPD patients and 0.79 (95% CI 0.71-0.87) for the asthmatics, relative to the bronchiectatic patients. Bronchiectasis was the main cause of death in 13% of bronchiectatic patients, the risk of death being increased by a factor of 1.21 in the presence of asthma as the main secondary diagnosis, by 1.31 with COPD, by 1.35 with tuberculosis and its sequelae, and by 1.32 with some other secondary diagnosis, as compared with cases for which no secondary diagnosis was indicated. The fact that the prognosis for bronchiectatic patients is poorer than that for asthmatics points to a continued need for focused care and follow-up, particularly in the presence of additional illnesses.
KSHV vFLIP Is Essential for the Survival of Infected Lymphoma Cells
Authors: Ilaria Guasparri, Shannon A. Keller, Ethel Cesarman
Journal: The Journal of Experimental Medicine (2004)

Primary effusion lymphomas (PELs) associated with infection by the Kaposi's sarcoma–associated herpesvirus (KSHV/HHV-8) have constitutive nuclear factor (NF)–κB activity that is essential for their survival, but the source of this activity is unknown. We report that viral FADD-like interleukin-1-β–converting enzyme [FLICE/caspase 8]-inhibitory protein (FLIP) activates NF-κB more potently than cellular FLIP in B cells and that it is largely responsible for NF-κB activation in latently infected PEL cells. Elimination of vFLIP production in PEL cells by RNA interference results in significantly decreased NF-κB activity, down-regulation of essential NF-κB–regulated cellular prosurvival factors, induction of apoptosis, and enhanced sensitivity to external apoptotic stimuli. vFLIP is the first virally encoded gene shown to be essential for the survival of naturally infected tumor cells.
Enhanced renal prostaglandin production in the dog. II. Effects on intrarenal hemodynamics.
Authors: L C Chang, J A Splawinski, J A Oates, A S Nies
Journal: Circulation Research (1975)

The effects of enhanced endogenous production of prostaglandins by the kidney on the distribution of blood flow in the renal cortex were assessed by infusing sodium arachidonate, the precursor of the renal prostaglandins, into one renal artery of the dog. The changes produced with arachidonate (3 times 10--6 g/kg min-1 and 10--5 g/kg min--1) were compared with those produced by infusions of prostaglandin (PG) E2 (10--7 g/kg min--1) and PGF2alpha (3 times 10--7 g/kg min--1) into one renal artery. Distribution of renal blood flow was measured by the radioactive microsphere technique. Sodium arachidonate caused an increase in blood flow to the inner cortical zones with no change in flow to the nephrons in the outermost quarter of the cortex. PGE2 increased flow to all cortical zones, and PGF2alpha produced no change in flow. Since arterial blood pressure did not change, changes in vascular resistance were reciprocal to changes in flow. Thus, vascular resistance fell in the inner cortical regions but not in the outer regions, with arachidonate infusions and in all regions of the cortex with PGE2 infusions; no changes were seen with PGF2alpha infusions. These data indicate that prostaglandin formed endogenously in the kidney affects the vascular resistance of only the inner cortical nephrons; the data thus support the hypothesis that renal prostaglandins are one mediator of renal autoregulation of blood flow.
Purifying Selection Modulates the Estimates of Population Differentiation and Confounds Genome-Wide Comparisons across Single-Nucleotide Polymorphisms
Authors: T. Maruki, S. Kumar, Y. Kim
Journal: Molecular Biology and Evolution (2012)

An improved understanding of the biological and numerical properties of measures of population differentiation across loci is becoming increasingly more important because of their growing use in analyzing genome-wide polymorphism data for detecting population structures, inferring the rates of migration, and identifying local adaptations. In a genome-wide analysis, we discovered that the estimates of population differentiation (e.g., FST, θ, and Jost's D) calculated for human single-nucleotide polymorphisms (SNPs) are strongly and positively correlated to the position-specific evolutionary rates measured from multispecies alignments. That is, genomic positions (loci) experiencing higher purifying selection (lower evolutionary rates) produce lower values for the degree of population differentiation than those evolving with faster rates. We show that this pattern is completely mediated by the negative effects of purifying selection on the minor allele frequency (MAF) at individual loci. Our results suggest that inferences and methods relying on the comparison of population differentiation estimates (FST, θ, and Jost's D) based on SNPs across genomic positions should be restricted to loci with similar MAFs and/or the rates of evolution in genome scale surveys.
The effect of prolonged endurance exercise upon blood pressure regulation during a postexercise orthostatic challenge
Authors: S E Privett, K P George, N Middleton, G P Whyte, N T Cable
Journal: British Journal of Sports Medicine (2008)

Objective To investigate the regulation of blood pressure in response to an orthostatic challenge in athletes running a marathon. Methods 10 experienced male runners (mean (SD) age 29 (4) years) were tested on the day prior to the 2004 London Marathon, and again immediately postrace (race time 210 (36) min). In addition, 6 of the subjects were retested 24 h postrace. During each examination, beat-to-beat systolic arterial blood pressure (SBP) and heart rate (HR) were measured, and stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were estimated via arterial transmural pressure waveforms during 3 min in a supine position and then during 3 min of upright, unsupported standing. Data were averaged over 20 s epochs, and the final 20 s of each posture were compared prerace and postrace via repeated measures 2-way ANOVA. Results Prerace SBP in standing increased only moderately when compared with supine values (2 (9) mm Hg, NS). This was accompanied by an increase in HR (13 (7) beats/min, p&lt;0.05), as well as a decrease in SV (16 (9) ml, p&lt;0.05). However, there was little change in CO (−0.13 (0.97) litres/min, NS) or TPR (0.047 (0.280) medical units (MU), NS). Postrace SBP significantly decreased from supine to standing (−15 (20) mm Hg, p&lt;0.05). The change in SBP was accompanied by an increase in HR (19 (6) beats/min, p&lt;0.05) and a reduction in SV (26 (14) ml, p&lt;0.05) and CO (−1.02 (1.39) litres/min, p = 0.05). Postrace there was no change in TPR (0.366 (0.607) MU, NS) upon standing. The orthostatic adjustments in SBP, HR and CO were greater than at prerace (p&lt;0.05). The postrace orthostatic challenge resulted in only one subject experiencing presyncopal symptoms. At 24 h postrace, cardiovascular responses to an orthostatic challenge mirrored those at prerace. Conclusions Following prolonged exercise, a fall in systolic blood pressure during orthostasis results from an inadequately compensated decrease in SV and resultant CO during standing.
Molecular divergence and phylogeny: rates and patterns of cytochrome b evolution in cranes
Authors: C. Krajewski, D. G. King
Journal: Molecular Biology and Evolution (1996)

Analyses of complete cytochrome b sequences from all species of cranes (Aves: Gruidae) reveal aspects of sequence evolution in the early stages of divergence. These DNA sequences are > or = 89% identical, but expected departures from random substitution are evident. Silent, third-position pyrimidine transitions are the dominant substitution type, with transversion comprising only a small fraction of sequence differences. Substitution patterns are not clearly manifested until divergence has reached a moderate level (> 3%), as expected for a stochastic process. Variation in the frequency of mismatch types among lineages decreases at larger divergences, but the level of bias does not decay. Divergence varies up to fivefold among gene regions but is not correlated with structural domain. All protein structural domains except extramembrane 4 display < 20% variable residues. Regions corresponding to putative functional domains show the excepted conservation of amino acids, although the C-terminal portion of the Q0 reaction center displays several nonconservative replacements. Phylogenetic analyses incorporating substitution asymmetries produced mixed results. Distances estimated with multiple parameters (transition, codon-position, composition, and pyrimidine-transition biases) yielded identical additive tree topologies with comparable bootstrap values, all consistent with uncontroversial species relationships. Maximum likelihood analysis incorporating these biases, as well as equally weighted parsimony analysis, produced similar results. Static, differential weighting for parsimony did not improve the phylogenetic signal but produced unusual trees with low bootstraps. The overall rate of nucleotide substitution varies slightly but significantly among cranes, and calibration of distances against fossil dates suggests divergence rates of 0.7%-1.7% per million years.
T-Cell Activation and Maturation at Tumor Site Associated With Objective Response to Ipilimumab in Metastatic Melanoma
Authors: Michele Del Vecchio, Roberta Mortarini, Gabrina Tragni, Lorenza Di Guardo, Ilaria Bersani, Giuseppe Di Tolla, Francesco Agustoni, Valentina Colonna, Jeffrey S. Weber, Andrea Anichini
Journal: Journal of Clinical Oncology (2011)
Sustained telomere length in hepatocytes and cholangiocytes with increasing age in normal liver
Authors: Suman Verma, Phaedra Tachtatzis, Sue Penrhyn-Lowe, Cinzia Scarpini, Diana Jurk, Thomas Von Zglinicki, Nick Coleman, Graeme J. M. Alexander
Journal: Hepatology (2012)

Telomeres, a validated biomarker of aging, comprise multiple nucleotide repeats capping chromosomes that shorten with each cell cycle until a critical length is achieved, precipitating cell senescence. Only two previous studies focused on the effect of aging in “normal” liver tissue, but these studies were compromised by small sample size, limited age range, tissue derived from individuals with an increased risk of senescence, and the use of liver homogenates. We developed a robust large-volume, four-color quantitative fluorescent in situ hybridization technique to measure telomere length in large numbers of hepatocytes, Kupffer cells, hepatic stellate cells, CD4-positive and CD8-positive lymphocytes, and cholangiocytes. Following validation against the gold standard (Southern blotting), the technique was applied to normal archived paraffin-embedded liver tissue obtained following reperfusion of implanted donor liver. We studied 73 highly selected donors aged 5-79 years with a short medical illness preceding death and no history of liver disease, reperfusion injury, or steatosis and normal graft function 1-year posttransplantation. Cholangiocytes had significantly longer telomeres compared with all other intrahepatic lineages over a wide age range ( P &lt; 0.05). Age-related telomere attrition was restricted to sinusoidal cells (i.e., Kupffer cells [ P = 0.0054] and stellate cells [ P = 0.0001]). Cholangiocytes and hepatocytes showed no age-related telomere shortening. Conclusion: In normal liver and over a broad age range, cholangiocytes have longer telomeres than all other intrahepatic lineages. Age-related telomere length decline is restricted to Kupffer cells and stellate cells. (Hepatology 2012)
Temperature drop can affect respiratory illness several days later
Authors: R. Robson
Journal: BMJ (2002)

The effects of cold weather on elderly patients can take up to 15 days to have an impact on GPs' consultation rates.

And each drop of 1° C below 5° C increases the number of consultations among elderly people for respiratory problems by 11%, compared with the average number of consultations two weeks before, according to new research. The researchers who did the study …
Severe salicylate poisoning treated conservatively
Authors: S. Basavarajaiah, P. Sigston, K. Budack
Journal: Journal of the Royal Society of Medicine (2004)

documented 2 and is presumed to be due to a vascular event in utero or infancy.In such cases, however, it is important to be aware that the testis may be in a different position. 3 On the macroscopic level it is vital to be aware that residual epididymal and vas deferens tissue may undergo cystic changes with time and hence an inguinal mass observed at surgery may mimic but not represent a testis.Furthermore, such tissue may be associated with a symptomless intraabdominal testis which may or may not be hypoplastic.Such tissue must be recognized and removed since, as in case 1, it can undergo malignant change.When a mass that is clinically an undescended testis shows no histologically proven testicular tissue we advocate further imaging and consideration of laparoscopy.
P55. Dendritic cell vaccination for postremission therapy in AML
Authors: FS Lichtenegger, B Beck, I Bigalke, C Geiger, W Hiddemann, R Henschler, G Kvalheim, DJ Schendel, M Subklewe
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Cellular immunotherapy is a highly effective treatment option for patients with acute myeloid leukaemia (AML) as shown by the low relapse rate after allogeneic stem cell transplantation. However, many patients are not eligible for this treatment. This has lead to the development
Dengue virus infections in travellers returning from Benin to France, July-August 2010
Authors: P Gautret, E Botelho-Nevers, R N Charrel, P Parola
Journal: Eurosurveillance (2010)

In July and August 2010, two cases of dengue fever were diagnosed in travellers returning from Benin to France. These two cases exemplify that dengue fever should be considered in febrile travellers, even those returning from areas where the infection is not usual.
Systemic plasmacytosis with cutaneous manifestations in a white man: Successful therapy with cyclophosphamide/prednisone
Authors: William P. Carey, M.Joyce Rico, MaryLynn Nierodzik, Gurdip Sidhu
Journal: Journal of the American Academy of Dermatology (1998)

Plasmacytosis is a rare disorder that occurs mainly in the Asian population; it is characterized by a polyclonal proliferation of plasma cells and hypergammaglobulinemia. There are two variants: cutaneous plasmacytosis with involvement limited to the skin and systemic plasmacytosis described by Watanabe et al.1 defined as involvement of two or more organ systems. In the Caucasian population, there has been one patient with cutaneous plasmacytosis reported from Spain2 and a patient from Switzerland of unknown race that conforms to the description of Watanabe et al. of systemic plasmacytosis.3 We describe what we believe to be the second case of systemic plasmacytosis in a white patient.
Canine Papilloma: Progression of Oral Papilloma to Carcinoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A M Watrach, E Small, M T Case
Journal: JNCI Journal of the National Cancer Institute (1970)

Squamous cell carcinoma was found in association with extensive and progressive oral papillomas in a 1½-year-old male beagle. The neoplasm was in the region of the posterior portion of the right jaw and evidently originated from the adjacent papillomatous growths. Possible relationship between the duration and extent of papillomatosis and the appearance of malignant change, heretofore not reported, is discussed.
Essential role of caspase-8 in p53/p73-dependent apoptosis induced by etoposide in head and neck carcinoma cells
Authors: Juan Liu, Hiroshi Uematsu, Nobuo Tsuchida, Masa-Aki Ikeda
Journal: Molecular Cancer (2011)

Abstract Background Caspase-8 is a key upstream mediator in death receptor-mediated apoptosis and also participates in mitochondria-mediated apoptosis via cleavage of proapoptotic Bid. However, the role of caspase-8 in p53- and p73-dependent apoptosis induced by genotoxic drugs remains unclear. We recently reported that the reconstitution of procaspase-8 is sufficient for sensitizing cisplatin- but not etoposide-induced apoptosis, in chemoresistant and caspase-8 deficient HOC313 head and neck squamous cell carcinoma (HNSCC) cells. Results We show that p53/p73-dependent caspase-8 activation is required for sensitizing etoposide-induced apoptosis by utilizing HOC313 cells carrying a temperature-sensitive p53G285K mutant. Restoration of wild-type p53 function under the permissive conditions, together with etoposide treatment, led to substantial transcriptional activation of proapoptotic Noxa and PUMA, but failed to induce apoptosis. In addition to p53 restoration, caspase-8 reconstitution was needed for sensitization to etoposide-induced apoptosis, mitochondria depolarization, and cleavage of the procaspases-3, and -9. In etoposide-sensitive Ca9-22 cells carrying a temperature-insensitive mutant p53, siRNA-based p73 knockdown blocked etoposide-induced apoptosis and procaspase-8 cleavage. However, induction of p73 protein and up-regulation of Noxa and PUMA, although observed in Ca9-22 cells, were hardly detected in etoposide-treated HOC313 cells under non-permissive conditions, suggesting a contribution of p73 reduction to etoposide resistance in HOC313 cells. Finally, the caspase-9 inhibitor Ac-LEHD-CHO or caspase-9 siRNA blocked etoposide-induced caspase-8 activation, Bid cleavage, and apoptosis in both cell lines, indicating that p53/p73-dependent caspase-8 activation lies downstream of mitochondria. Conclusions we conclude that p53 and p73 can act as upstream regulators of caspase-8, and that caspase-8 is an essential mediator of the p53/p73-dependent apoptosis induced by etoposide in HNSCC cells. Our data suggest the importance of caspase-8-mediated positive feedback amplification in the p53/p73-dependent apoptosis induced by etoposide in HNSCC cells.
Epidemiological and clinical aspects of tuberculosis pleurisies
Authors: Rachida Yahiaoui, Rabah Amrane
Journal: European Respiratory Journal (2013)

Introduction: Tuberculous pleurisy occupies the 2nd place of extra pulmonary tuberculosis pulmonary after the adenitis tuberculosis.  Objective: Describe epidemiological and clinical profile of tuberculous pleurisies through the experience of our pneumology department center.  Patients and Methods: Reporting us a cohort study concerning all cases of serofibrinous pleurisies diagnosed as tuberculosis brought together in day hospital between December, 2012 to January 2013  Results: 128 cases cases of serofibrinous pleurisies among which 74 cases (57%) are of tuberculous origin. Sex ratio showed 42 men (56%) and 32 women (44%) with a mean age of 45 years old (16-80). Revealing clinical signs are cough, dyspnoea and chest pain. Contagious is found in 20%. Chest X-ray objectifies pleura opacity in the right (65%), in the left (31%) and bilateral (4%). All patients benefited from an IDR in the tuberculin which positivity is observed in 63%. Exploratory pleural draining having returned a yellow liquid (90%), sero-hematic (9%) and chylous (1%). Pleural biopsy blind systematically realized and with have requiring to pleuroscopy at 3 patients (4%). Tuberculosis pleurisy was confirmed in 61,29% by the pleural biopsy, 3.32 %, by culture of the pleural bioptic fragment and 2 others case (3.22 %) in the culture of the pleural liquid and 20 cases are presumed (32.22%). All patients received a treatment bacillary anti 2RHZ / 4RH associated with pleural evacuating draining and with respiratory physiotherapy. Evolution was favorable in 96%.  Conclusion: According to the epidemiological data, tuberculosis remains the most frequent cause of pleural pathology in not developing countries estimated about 30% of extapulmonary tuberculosis.