tbuckley/cabot-search huggingface dataset:
DCAMKL-1 Regulates Epithelial–Mesenchymal Transition in Human Pancreatic Cells through a <i>miR-200a</i>–Dependent Mechanism
Authors: Sripathi M. Sureban, Randal May, Stan A. Lightfoot, Aimee B. Hoskins, Megan Lerner, Daniel J. Brackett, Russell G. Postier, Rama Ramanujam, Altaf Mohammed, Chinthalapally V. Rao, James H. Wyche, Shrikant Anant, Courtney W. Houchen
Journal: Cancer Research (2011)

Abstract Pancreatic cancer is an exceptionally aggressive disease in great need of more effective therapeutic options. Epithelial–mesenchymal transition (EMT) plays a key role in cancer invasion and metastasis, and there is a gain of stem cell properties during EMT. Here we report increased expression of the putative pancreatic stem cell marker DCAMKL-1 in an established KRAS transgenic mouse model of pancreatic cancer and in human pancreatic adenocarcinoma. Colocalization of DCAMKL-1 with vimentin, a marker of mesenchymal lineage, along with 14-3-3 σ was observed within premalignant PanIN lesions that arise in the mouse model. siRNA-mediated knockdown of DCAMKL-1 in human pancreatic cancer cells induced microRNA miR-200a, an EMT inhibitor, along with downregulation of EMT-associated transcription factors ZEB1, ZEB2, Snail, Slug, and Twist. Furthermore, DCAMKL-1 knockdown resulted in downregulation of c-Myc and KRAS through a let-7a microRNA-dependent mechanism, and downregulation of Notch-1 through a miR-144 microRNA-dependent mechanism. These findings illustrate direct regulatory links between DCAMKL-1, microRNAs, and EMT in pancreatic cancer. Moreover, they demonstrate a functional role for DCAMKL-1 in pancreatic cancer. Together, our results rationalize DCAMKL-1 as a therapeutic target for eradicating pancreatic cancers. Cancer Res; 71(6); 2328–38. ©2011 AACR.
Many US faculty members on institutional review boards have ties with industry
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

A study of US medical schools' faculty members serving on institutional review boards found that industry funding is common. About half of review board members are faculty members and about half of these have industry ties ( Academic Medicine 2003;78:1-6)

The boards aim to protect patients in clinical research studies by reviewing the protocols before a study begins, approving changes in an ongoing study, and responding to reports of adverse events.

“Industry funding is part of the modern scientific enterprise. It's a fact of life. Universities should manage [the relationships] to guard against risks and realise …
Costs and Consequences Associated With Newer Medications for Glycemic Control in Type 2 Diabetes
Authors: Anushua Sinha, Mangala Rajan, Thomas Hoerger, Len Pogach
Journal: Diabetes Care (2010)

OBJECTIVE Newer medications offer more options for glycemic control in type 2 diabetes. However, they come at considerable costs. We undertook a health economic analysis to better understand the value of adding two newer medications (exenatide and sitagliptin) as second-line therapy to glycemic control strategies for patients with new-onset diabetes. RESEARCH DESIGN AND METHODS We performed a cost-effectiveness analysis for the U.S. population aged 25–64. A lifetime analytic horizon and health care system perspective were used. Costs and quality-adjusted life years (QALYs) were discounted at 3% annually, and costs are presented in 2008 U.S. dollars. We compared three glycemic control strategies: 1) glyburide as a second-line agent, 2) exenatide as a second-line agent, and 3) sitagliptin as a second-line agent. Outcome measures included QALYs gained, incremental costs, and the incremental cost-effectiveness ratio associated with each strategy. RESULTS Exenatide and sitagliptin conferred 0.09 and 0.12 additional QALYs, respectively, relative to glyburide as second-line therapy. In base case analysis, exenatide was dominated (cost more and provided fewer QALYs than the next most expensive option), and sitagliptin was associated with an incremental cost-effectiveness ratio of $169,572 per QALY saved. Results were sensitive to assumptions regarding medication costs, side effect duration, and side effect–associated disutilities. CONCLUSIONS Exenatide and sitagliptin may confer substantial costs to health care systems. Demonstrated gains in quality and/or quantity of life are necessary for these agents to provide economic value to patients and health care systems.
A genomic approach to investigate developmental cell death in woody tissues of Populus trees.
Authors: Charleen Moreau, Nikolay Aksenov, Maribel García Lorenzo, Bo Segerman, Christiane Funk, Peter Nilsson, Stefan Jansson, Hannele Tuominen
Journal: Genome biology (2005)

Abstract Background Poplar ( Populus sp.) has emerged as the main model system for molecular and genetic studies of forest trees. A Populus expressed sequence tag (EST) database (POPULUSDB) was previously created from 19 cDNA libraries each originating from different Populus tree tissues, and opened to the public in September 2004. We used this dataset for in silico transcript profiling of a particular process in the woody tissues of the Populus stem: the programmed death of xylem fibers. Results One EST library in POPULUSDB originates from woody tissues of the Populus stem where xylem fibers undergo cell death. Analysis of EST abundances and library distribution within the POPULUSDB revealed a large number of previously uncharacterized transcripts that were unique in this library and possibly related to the death of xylem fibers. The in silico analysis was complemented by a microarray analysis utilizing a novel Populus cDNA array with a unigene set of 25,000 sequences. Conclusions In silico analysis, combined with the microarray analysis, revealed the usefulness of non-normalized EST libraries in elucidating transcriptional regulation of previously uncharacterized physiological processes. The data suggested the involvement of two novel extracellular serine proteases, nodulin-like proteins and an Arabidopsis thaliana OPEN STOMATA 1 ( AtOST1 ) homolog in signaling fiber-cell death, as well as mechanisms responsible for hormonal control, nutrient remobilization, regulation of vacuolar integrity and autolysis of the dying fibers.
2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial
Authors: Christoph C Lees, Neil Marlow, Aleid van Wassenaer-Leemhuis, Birgit Arabin, Caterina M Bilardo, Christoph Brezinka, Sandra Calvert, Jan B Derks, Anke Diemert, Johannes J Duvekot, Enrico Ferrazzi, Tiziana Frusca, Wessel Ganzevoort, Kurt Hecher, Pasquale Martinelli, Eva Ostermayer, Aris T Papageorghiou, Dietmar Schlembach, K T M Schneider, Baskaran Thilaganathan, Tullia Todros, Adriana Valcamonico, Gerard H A Visser, Hans Wolf
Journal: The Lancet (2015)
Use of Arsenic Trioxide (As2O3 ) in the Treatment of Acute Promyelocytic Leukemia (APL): II. Clinical Efficacy and Pharmacokinetics in Relapsed Patients
Authors: Zhi-Xiang Shen, Guo-Qiang Chen, Jian-Hua Ni, Xiu-Shong Li, Shu-Min Xiong, Qian-Yao Qiu, Jun Zhu, Wei Tang, Guan-Lin Sun, Kan-Qi Yang, Yu Chen, Li Zhou, Zhi-Wen Fang, Yan-Ting Wang, Jun Ma, Peng Zhang, Ting-Dong Zhang, Sai-Juan Chen, Zhu Chen, Zhen-Yi Wang
Journal: Blood (1997)
Stem Cell Treatments Raise Thorny Questions for Researchers, Clinicians
Authors: K. Hede
Journal: JNCI Journal of the National Cancer Institute (2012)

has proliferated in recent years and is gaining in popularity as high-profile professional athletes and prominent public fi gures have opted for stem cell treatments. Now some professional organizations and individual scientists are arguing that it ’ s time for stem cell researchers to speak out against unproven medical practices involving stem cells — or risk losing the public ’ s trust. “There ’ s this gray area of medical innovation,” said Lawrence Goldstein, Ph.D., director of the University of California, San Diego, Stem Cell Research Program and chair of SCRM ’ s scientifi c research steering committee. Goldstein, who helped write Proposition 71, in which California funded $3 billion in human stem cell research, noted that squashing medical innovation by restricting physicians ’ ability to innovate within their profession benefi ts no one. However, “if it becomes systematic, then it starts to look a lot like research versus innovation, and that ’ s regulated. The question is, what do you do in that gray area?” That ’ s where state medical boards come in. Without federal regulation on stem cell treatments, some state medical boards are stepping in to regulate stem cells ’ medical use. The Texas Medical Board is debating new rules that would require a stateappointed panel to review safety procedures for any proposed new stem cell therapy. The review was prompted by a report that Gov. Rick Perry had stem cells isolated from his own fat injected into his back during a spinal fusion procedure in Texas.
Short burst oxygen therapy for relief of breathlessness in COPD
Authors: C M Roberts
Journal: Thorax (2004)

More evidence against the effect of short burst oxygen therapy, but doubts remain

In this issue of Thorax Stevenson and Calverley1 provide more evidence for a lack of effect of short burst oxygen therapy in the relief of dyspnoea following exercise in patients with chronic obstructive pulmonary disease (COPD). This study follows other recent publications that appear to draw the same conclusion. Despite this mounting evidence, oxygen cylinders for “as needed” use are still frequently prescribed at great cost.2,3 Oxygen used in this way is often perceived as life saving by patients, but can this continuing practice of short burst oxygen use for COPD patients be justified in the light of the emerging evidence?

Oxygen therapy for the management of chronic COPD comes in various forms. Long term oxygen therapy (LTOT) prescribing has an accepted evidence base and any patient considered for short burst treatment should first have undergone an assessment for LTOT. Ambulatory oxygen has been shown to have some beneficial effect in some patients researched in a number of studies that demonstrate some concordance. It is a continuing challenge to the respiratory establishment, however, that the form of oxygen most commonly prescribed in the UK lacks such an agreed evidence base. Short burst oxygen use for the palliation of dyspnoea is fairly widespread among patients with severe COPD.2 Anecdotally, it is beloved by them and often given at their request by respiratory specialists and general practitioners when other options have been exhausted. When it is given there is some evidence that it is used inconsistently4—either before or after exercise—and that the delivery mode is non-standardised with both face masks and nasal cannulae being used with flow rates set usually at 2 or 4 l/min, but often left to the discretion of the …
Non-fatal acute fatty liver of pregnancy.
Authors: J Bernuau, C Degott, O Nouel, B Rueff, J P Benhamou
Journal: Gut (1983)

Four patients are described, admitted during a three-year period, who recovered from acute fatty liver of pregnancy; vomiting and jaundice were the main manifestations of the disease; coma and anuria were absent. During the same period, we observed one patient who died of acute fatty liver of pregnancy. This experience suggests that the non-fatal form of the disorder may be much commoner than the fatal form.
Use of field-based tests to identify risk factors for injury to fast bowlers in cricket
Authors: R J Dennis, C F Finch, A S McIntosh, B C Elliott
Journal: British Journal of Sports Medicine (2008)

Objective: To identify risk factors for injury to cricket fast bowlers using field-based tests. Design: Prospective cohort study. Setting: High performance Australian cricket. Participants: Ninety-one male adolescent and adult fast bowlers (aged 12–33 years). Assessment of risk factors: A field-based pre-participation screening, consisting of musculoskeletal, fitness and anthropometric assessments and analysis of bowling technique was undertaken. Bowlers were prospectively monitored over the 2003–4 season and bowling workload and injuries were recorded. Logistic regression was used to identify injury risk factors. Main outcome measurement: Repetitive microtrauma injury to the trunk, back or lower limb associated with fast bowling. Results: Two variables were identified as independent predictors of injury in the multivariate logistic regression analysis. Bowlers with hip internal rotation of ⩽30° on the leg ipsilateral to the bowling arm were at a significantly reduced risk of injury (OR 0.20, 95% CI 0.06 to 0.73) compared with bowlers with &gt;40° of rotation. Bowlers with an ankle dorsiflexion lunge of 12.1–14.0 cm on the leg contralateral to the bowling arm were at a significantly increased risk (OR 4.03, 95% CI 1.07 to 15.21) than bowlers with a lunge of &gt;14 cm. Bowlers with a lunge of ⩽12 cm were also at an increased risk, but not significantly so (OR 1.38, 95% CI 0.40 to 4.84). Conclusions: Biomechanical research is needed to investigate how these two intrinsic risk factors increase injury risk so that appropriate interventions can be developed.
The fibrin-derived γ377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease
Authors: Ryan A. Adams, Jan Bauer, Matthew J. Flick, Shoana L. Sikorski, Tal Nuriel, Hans Lassmann, Jay L. Degen, Katerina Akassoglou
Journal: The Journal of Experimental Medicine (2007)

Perivascular microglia activation is a hallmark of inflammatory demyelination in multiple sclerosis (MS), but the mechanisms underlying microglia activation and specific strategies to attenuate their activation remain elusive. Here, we identify fibrinogen as a novel regulator of microglia activation and show that targeting of the interaction of fibrinogen with the microglia integrin receptor Mac-1 (αMβ2, CD11b/CD18) is sufficient to suppress experimental autoimmune encephalomyelitis in mice that retain full coagulation function. We show that fibrinogen, which is deposited perivascularly in MS plaques, signals through Mac-1 and induces the differentiation of microglia to phagocytes via activation of Akt and Rho. Genetic disruption of fibrinogen–Mac-1 interaction in fibrinogen-γ390-396A knock-in mice or pharmacologically impeding fibrinogen–Mac-1 interaction through intranasal delivery of a fibrinogen-derived inhibitory peptide (γ377-395) attenuates microglia activation and suppresses relapsing paralysis. Because blocking fibrinogen–Mac-1 interactions affects the proinflammatory but not the procoagulant properties of fibrinogen, targeting the γ377-395 fibrinogen epitope could represent a potential therapeutic strategy for MS and other neuroinflammatory diseases associated with blood-brain barrier disruption and microglia activation.
Tranexamic acid and upper gastrointestinal haemorrhage--a double-blind trial.
Authors: J C Biggs, T B Hugh, A J Dodds
Journal: Gut (1976)

The efficacy of antifibrinolytic therapy in the management of acute upper gastrointestinal haemorrhage has been investigated in a double-blind clinical trial. Two-hundred patients were studied using tranexamic acid, a potent antifibrinolytic agent. Of these, 103 were in the treatment group and 97 in the control group. Patients were analysed to determine severity of initial blood loss, transfusion requirements, together with the incidence of recurrent bleeding, surgical intervention, and death. Final diagnosis as to the site of bleeding was arrived at using endoscopy, barium studies, and the findings at operation and necropsy. The groups were well matched as regards severity of initial haemorrhage, age, sex, aetiological diagnosis, and precipitating factors. A significant difference was observed in the requirement for surgical intervention to control continuing or recurrent haemorrhage. Twenty-three of 97 in the control group and seven of 103 in the treatment group required surgery. There appeared to be a reduction in the transfusion rate after the first three days of hospitalization in the treatment group. There were no significant differences in mortality or in side-effects between the two groups.
Expenditures and Health Status Among Adults With Back and Neck Problems
Authors: Brook I. Martin
Journal: JAMA (2008)

<h3>Context</h3>Back and neck problems are among the symptoms most commonly encountered in clinical practice. However, few studies have examined national trends in expenditures for back and neck problems or related these trends to health status measures.<h3>Objectives</h3>To estimate inpatient, outpatient, emergency department, and pharmacy expenditures related to back and neck problems in the United States from 1997 through 2005 and to examine associated trends in health status.<h3>Design and Setting</h3>Age- and sex-adjusted analysis of the nationally representative Medical Expenditure Panel Survey (MEPS) from 1997 to 2005 using complex survey regression methods. The MEPS is a household survey of medical expenditures weighted to represent national estimates. Respondents were US adults (&gt; 17 years) who self-reported back and neck problems (referred to as “spine problems” based on MEPS descriptions and International Classification of Diseases, Ninth Revision, Clinical Modification definitions).<h3>Main Outcome Measures</h3>Spine-related expenditures for health services (inflation-adjusted); annual surveys of self-reported health status.<h3>Results</h3>National estimates were based on annual samples of survey respondents with and without self-reported spine problems from 1997 through 2005. A total of 23 045 respondents were sampled in 1997, including 3139 who reported spine problems. In 2005, the sample included 22 258 respondents, including 3187 who reported spine problems. In 1997, the mean age- and sex-adjusted medical costs for respondents with spine problems was $4695 (95% confidence interval [CI], $4181-$5209), compared with $2731 (95% CI, $2557-$2904) among those without spine problems (inflation-adjusted to 2005 dollars). In 2005, the mean age- and sex- adjusted medical expenditure among respondents with spine problems was $6096 (95% CI, $5670-$6522), compared with $3516 (95% CI, $3266-$3765) among those without spine problems. Total estimated expenditures among respondents with spine problems increased 65% (adjusted for inflation) from 1997 to 2005, more rapidly than overall health expenditures. The estimated proportion of persons with back or neck problems who self-reported physical functioning limitations increased from 20.7% (95% CI, 19.9%-21.4%) to 24.7% (95% CI, 23.7%-25.6%) from 1997 to 2005. Age- and sex-adjusted self-reported measures of mental health, physical functioning, work or school limitations, and social limitations among adults with spine problems were worse in 2005 than in 1997.<h3>Conclusions</h3>In this survey population, self-reported back and neck problems accounted for a large proportion of health care expenditures. These spine-related expenditures have increased substantially from 1997 to 2005, without evidence of corresponding improvement in self-assessed health status.
Dialysis adequacy and nutrition determine prognosis in continuous ambulatory peritoneal dialysis patients.
Authors: L Fung, C A Pollock, R J Caterson, J F Mahony, D A Waugh, C Macadam, L S Ibels
Journal: Journal of the American Society of Nephrology (1996)

Peritoneal membrane function was assessed in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using parameters derived from urea kinetic modeling and the peritoneal equilibration test (PET). Their relationships with other nutritional markers and overall morbidity were determined. Data regarding the patients' nutritional status as determined by total body nitrogen (TBN) measurements, hospital admissions, and infectious complications within the last 12 months were reviewed. Total dialysate clearance (Kt/V) delivered was highly dependent on residual renal function (P < 0.0001). Kt/V derived from peritoneal clearance diminished with increasing age (P < 0.05). A higher delivered total Kt/V was associated with higher normalized protein catabolic rates (P < 0.002), which in turn were associated with improved TBN (P < 0.05). Hospital admissions decreased with improved normalized protein catabolic rates (P < 0.05), and higher serum albumin and total protein levels (P < 0.01 and P < 0.002, respectively). Infectious complications correlated positively with time on dialysis (P < 0.01), and correlated negatively with TBN measurements (P = 0.05). No correlations were found between infectious complications and serum albumin level or peritoneal protein loss. However, the total duration of hospitalization was shortened with higher serum albumin and total protein levels (P < 0.0001 and P < 0.002, respectively). Although Kt/V determinations did not correlate with clearances determined by the PET, the PET-determined creatinine transport rate correlated with TBN (P < 0.05) but not with infectious complications. In conclusion, nutritional parameters correlate with outcome on continuous ambulatory peritoneal dialysis. An integral relationship exists between nutritional status and dialysis delivery, which is best assessed by urea kinetic modeling.
Allium Vegetables and Risk of Prostate Cancer: A Population-Based Study
Authors: A. W. Hsing
Journal: JNCI Journal of the National Cancer Institute (2002)

Epidemiologic and laboratory studies suggest that allium vegetables and garlic constituents have antitumor effects. In a population-based, case–control study conducted in Shanghai, China, we investigated the association between intake of allium vegetables, including garlic, scallions, onions, chives, and leeks, and the risk of prostate cancer. We administered in-person interviews and collected information on 122 food items from 238 case subjects with incident, histologically confirmed prostate cancer and from 471 male population control subjects. Men in the highest of three intake categories of total allium vegetables (>10.0 g/day) had a statistically significantly lower risk (odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.76; Ptrend<.001) of prostate cancer than those in the lowest category (<2.2 g/day). Similar comparisons between categories showed reductions in risk for men in the highest intake categories for garlic (OR = 0.47, 95% CI = 0.31 to 0.71; Ptrend<.001) and scallions (OR = 0.30, 95% CI = 0.18 to 0.51; Ptrend<.001). The reduced risk of prostate cancer associated with allium vegetables was independent of body size, intake of other foods, and total calorie intake and was more pronounced for men with localized than with advanced prostate cancer.
Shin splints--a literature review.
Authors: P Bates
Journal: British Journal of Sports Medicine (1985)

"Shin splints" is not a specific diagnosis. It is merely a descriptive term that describes chronic exertional shin pain in an athlete. The evidence seems clear that shin splint pain has many different causes and this reflects the variation in the anatomy. It would be preferable to describe shin splint pain by location and aetiology, for example, lower medial tibial pain due to periostitis or upper lateral tibial pain due to elevated compartment pressure. This would aid communication between physicians and also direct therapy more accurately.