tbuckley/cabot-search huggingface dataset:
Elevated Serum Insulin-Like Growth Factor Binding Protein-2 as a Prognostic Marker in Patients with Ovarian Cancer
Authors: Sally Baron-Hay, Frances Boyle, Alan Ferrier, Carolyn Scott
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this research was to examine the diagnostic and prognostic significance of elevated serum insulin-like growth factor binding protein (IGFBP)-2 levels in women with ovarian cancer from diagnosis through treatment to relapse or remission. Experimental Design: Serum collected pre- and postoperatively in women newly diagnosed with ovarian cancer, during adjuvant chemotherapy cycles, at 6 months follow-up and at relapse was analyzed for IGFBP-2. Control serum was from women undergoing pelvic or abdominal surgery for benign ovarian disease or nonovarian pathology. Results: IGFBP-2 at diagnosis was significantly elevated (P &amp;lt; 0.0001) in women with ovarian cancer (887 ± 62 ng/ml) compared with benign controls (337 ± 25 ng/ml), and women undergoing nonovarian surgery (439 ± 49 ng/ml) and correlated positively with tumor stage and cellular differentiation but not with CA125. Unexpectedly, IGFBP-2 levels increased additionally 1-week postoperatively in ovarian cancer patients (1581 ± 90 ng/ml; P = 0.0027) as well as controls (977 ± 95 ng/ml; P &amp;lt; 0.0001) and was higher in women who had suboptimal debulking compared with optimal debulking of their tumor. IGFBP-2 levels returned to normal in women without evidence of progressive disease, but remained significantly elevated in women who later relapsed. Patients with IGFBP-2 levels in the highest tertile at diagnosis had a significantly shorter progression-free interval and overall survival. Conclusion: In ovarian cancer IGFBP-2 is elevated at diagnosis, and corresponds to stage and histology with patients in the highest tertile of IGFBP-2 more likely to relapse and have a poorer outlook. Identification of these patients at diagnosis may allow more individualized, aggressive adjuvant treatment and follow-up, and IGFBP-2 may therefore be an important additional prognostic marker in this disease.
TSC–mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species
Authors: Chong Chen, Yu Liu, Runhua Liu, Tsuneo Ikenoue, Kun-Liang Guan, Yang Liu, Pan Zheng
Journal: The Journal of Experimental Medicine (2008)

The tuberous sclerosis complex (TSC)–mammalian target of rapamycin (mTOR) pathway is a key regulator of cellular metabolism. We used conditional deletion of Tsc1 to address how quiescence is associated with the function of hematopoietic stem cells (HSCs). We demonstrate that Tsc1 deletion in the HSCs drives them from quiescence into rapid cycling, with increased mitochondrial biogenesis and elevated levels of reactive oxygen species (ROS). Importantly, this deletion dramatically reduced both hematopoiesis and self-renewal of HSCs, as revealed by serial and competitive bone marrow transplantation. In vivo treatment with an ROS antagonist restored HSC numbers and functions. These data demonstrated that the TSC–mTOR pathway maintains the quiescence and function of HSCs by repressing ROS production. The detrimental effect of up-regulated ROS in metabolically active HSCs may explain the well-documented association between quiescence and the “stemness” of HSCs.
Quality of Diabetes Care in U.S. Academic Medical Centers
Authors: Richard W. Grant, John B. Buse, James B. Meigs
Journal: Diabetes Care (2005)

OBJECTIVE— To assess both standard and novel diabetes quality measures in a national sample of U.S. academic medical centers. RESEARCH DESIGN AND METHODS— This retrospective cohort study was conducted from 10 January 2000 to 10 January 2002. It involved 30 U.S. academic medical centers, which contributed data from 44 clinics (27 primary care clinics and 17 diabetes/endocrinology clinics). For 1,765 eligible adult patients with type 1 or type 2 diabetes with at least two clinic visits in the 24 months before 10 January 2002, including one visit in the 6 months before 10 January 2002, we assessed measurement and control of HbA1c, blood pressure, and cholesterol and corresponding medical regimen changes at the most recent clinic visit. RESULTS— In this ethnically and economically diverse cohort, annual testing rates were very high (97.4% for HbA1c, 96.6% for blood pressure, and 87.6% for total cholesterol). Fewer patients were at HbA1c goal (34.0% &amp;lt;7.0%) or blood pressure goal (33.0% &amp;lt;130/80 mmHg) than lipid goals (65.1% total cholesterol &amp;lt;200 mg/dl, 46.1% with LDL cholesterol &amp;lt;100 mg/dl). Only 10.0% of the cohort met recommended goals for all three risk factors. At the most recent clinic visit, 40.4% of patients with HbA1c concentrations above goal underwent adjustment of their corresponding regimens. Among untreated patients, few with elevated blood pressure (10.1% with blood pressure &amp;gt;130/80 mmHg) or elevated LDL cholesterol (5.6% with LDL &amp;gt;100 mg/dl) were started on corresponding therapy. Patients with type 2 diabetes were no less likely to be intensified than patients with type 1 diabetes. CONCLUSIONS— High rates of risk factor testing do not necessarily translate to effective metabolic control. Low rates of medication adjustment among patients with levels above goal suggest a specific and novel target for quality improvement measurement.
Increased PTSD Risk With Combat-Related Injury: A Matched Comparison Study of Injured and Uninjured Soldiers Experiencing the Same Combat Events
Authors: Danny Koren, Doron Norman, Ayala Cohen, Jason Berman, Ehud M. Klein
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The aim of the present study was to isolate the unique contribution of physical injury to the subsequent development of posttraumatic stress disorder (PTSD). METHOD: Participants were 60 injured soldiers and a comparison group of 40 soldiers (matched by rank, military role, and length of service) who took part in the same combat situations but were not injured. Current and lifetime diagnoses were determined by using the Structured Clinical Interview for DSM-IV. In addition, an extensive battery of self-report questionnaires was given to assess severity of PTSD, anxiety, depression, and dissociative symptoms. The average time that elapsed between the injury and the interview was 15.5 months (SD=7.3). RESULTS: Ten (16.7%) of the 60 injured survivors but only one (2.5%) of the 40 comparison soldiers met diagnostic criteria for PTSD at the time of the interview (odds ratio=8.6, 95% confidence interval=1.1–394.3). Moreover, wounded participants had significantly higher scores than their noninjured counterparts on all clinical measures. Finally, presence of PTSD was not related to severity of injury or severity of the trauma. CONCLUSIONS: The findings clearly indicate that bodily injury is a major risk factor—rather than a protective one—for PTSD. While supporting the notion that bodily injury contributes to the appraisal of the traumatic event as more dangerous, the data also suggest that this heightened level of perceived threat is not a simple, straightforward function of the severity of injury or of the traumatic event.
The effect of surgery for symptomatic endometriosis: the other side of the story
Authors: P. Vercellini, P.G. Crosignani, A. Abbiati, E. Somigliana, P. Viganò, L. Fedele
Journal: Human Reproduction Update (2009)

Surgery is often considered the best treatment option in women with symptomatic endometriosis. However, extent and duration of the therapeutic benefit are still poorly defined. The best available evidence on surgery for endometriosis-associated pain has been reviewed to estimate the effect size of interventions in the most frequently encountered clinical conditions. Methodological drawbacks limit considerably the validity of observational, non-comparative studies on the effect of laparoscopy for stage I–IV disease. As indicated by the results of three RCTs, the absolute benefit increase of destruction of lesions compared with diagnostic only operation in terms of proportion of women reporting pain relief was between 30% and 40% after short follow-up periods. The effect size tended to decrease with time and the re-operation rate, based on long-term follow-up studies, was as high as 50%. In most case series on excisional surgery for rectovaginal endometriosis, substantial short-term pain relief was experienced by ∼70–80% of the subjects who continued the study. However, at 1 year follow-up, ∼50% of the women needed analgesics or hormonal treatments. Major complications were observed in 3–10% of the patients. Medium-term recurrence of lesions was observed in ∼20% of the cases, and around 25% of the women underwent repetitive surgery. Pain recurrence and re-operation rates after conservative surgery for symptomatic endometriosis are high and probably underestimated. Clinicians and patients should be aware that the expected benefit is operator-dependent.
Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors
Authors: A M Roque-Afonso, C Feray, D Samuel, D Simoneau, B Roche, J-F Emile, M Gigou, D Shouval, E Dussaix
Journal: Gut (2002)

Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors.Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis.Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4-39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post-transplantation (range 1-23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative.Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence.
Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial
Authors: David F Garway-Heath, David P Crabb, Catey Bunce, Gerassimos Lascaratos, Francesca Amalfitano, Nitin Anand, Augusto Azuara-Blanco, Rupert R Bourne, David C Broadway, Ian A Cunliffe, Jeremy P Diamond, Scott G Fraser, Tuan A Ho, Keith R Martin, Andrew I McNaught, Anil Negi, Krishna Patel, Richard A Russell, Ameet Shah, Paul G Spry, Katsuyoshi Suzuki, Edward T White, Richard P Wormald, Wen Xing, Thierry G Zeyen
Journal: The Lancet (2014)

Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo.In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140.We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug.This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period.Pfizer, UK National Institute for Health Research Biomedical Research Centre.
Head injuries among FIS World Cup alpine and freestyle skiers and snowboarders: a 7-year cohort study
Authors: Sophie E Steenstrup, Tone Bere, Roald Bahr
Journal: British Journal of Sports Medicine (2013)

Background Traumatic brain injury is the leading cause of death for skiers and snowboarders. Fatal head injuries have also occurred at the International Ski Federation (FIS) World Cup (WC) level. We therefore wanted to describe the risk of head injuries across disciplines and sex among WC skiers and snowboarders. Method We conducted retrospective interviews with FIS WC athletes at the end of seven consecutive seasons (2006–2013) to register injuries sustained during the competitive season. Head injuries were classified as ‘head/face’ injuries and did not include neck or cervical spine injuries. To calculate the exposure, we extracted data from the official FIS website for all WC competitions for each of the athletes interviewed. Results A total of 2080 injuries were reported during seven WC seasons. Of these, 245 (11.8%) were head/face injuries. Of the 245 head/face injuries reported, nervous system injuries/concussions were the most common (81.6%) and 58 of these were severe (23.7%). The injury incidence per 1000 competition runs was higher in freestyle (1.8, 95% CI 1.2 to 2.4) than in alpine skiing (0.9, 95% CI 0.6 to 1.2; risk ratio (RR) 2.05, 95% CI 1.25 to 3.46) and snowboard (1.0, 95% CI 0.6 to 1.3; RR 1.85, 95% CI 1.15 to 2.99). Women had a higher injury incidence (5.8, 95% CI 4.8 to 6.9) versus men (3.9, 95% CI 3.2 to 4.6; RR 1.48, 95% CI 1.15 to 1.90) throughout the season (per 100 athletes). Conclusions The majority of head/face injuries were nervous system injuries/concussions and one in four injuries was severe. Freestyle skiers had the highest overall head injury incidence. Across all disciplines, the injury incidence was higher in women than in men.
Clinical Significance of Programmed Death-1 Ligand-1 and Programmed Death-1 Ligand-2 Expression in Human Esophageal Cancer
Authors: Yuichiro Ohigashi, Masayuki Sho, Yukishige Yamada, Yoshikazu Tsurui, Kaoru Hamada, Naoya Ikeda, Takashi Mizuno, Ryo Yoriki, Hisanori Kashizuka, Katsunari Yane, Fumihiko Tsushima, Noriko Otsuki, Hideo Yagita, Miyuki Azuma, Yoshiyuki Nakajima
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The negative regulatory programmed death-1/programmed death-1 ligand (PD-1/PD-L) pathway in T-cell activation has been suggested to play an important role in tumor evasion from host immunity. In this study, we investigated the expression of PD-L1 and PD-L2 in human esophageal cancer to define their clinical significance in patients' prognosis after surgery. Experimental Design: PD-L1 and PD-L2 gene expression was evaluated in 41 esophagectomy patients by real-time quantitative PCR. The protein expression was also evaluated with newly generated monoclonal antibodies that recognize human PD-L1 (MIH1) and PD-L2 (MIH18). Results: The protein and the mRNA levels of determination by immunohistochemistry and real-time quantitative PCR were closely correlated. PD-L–positive patients had a significantly poorer prognosis than the negative patients. This was more pronounced in the advanced stage of tumor than in the early stage. Furthermore, multivariate analysis indicated that PD-L status was an independent prognostic factor. Although there was no significant correlation between PD-L1 expression and tumor-infiltrating T lymphocytes, PD-L2 expression was inversely correlated with tumor-infiltrating CD8+ T cells. Conclusions: These data suggest that PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with esophageal cancer and provide the rationale for developing novel immunotherapy of targeting PD-1/PD-L pathway.
In vitro correlate for a clonal deletion mechanism of immune response gene-controlled nonresponsiveness.
Authors: N Ishii, Z A Nagy, J Klein
Journal: The Journal of Experimental Medicine (1983)

We used T cell-antigen-presenting cell (APC) combinations from two pairs of recombinant mouse strains, B10.A(4R)-B10.A(2R) and B10.S(7R)-B10.S(9R) (abbreviated 4R, 2R, 7R, 9R, respectively), which differ from each other only in the nonexpression vs. expression of cell-surface E molecules, to study the mechanism of the Ir gene-controlled (E-restricted) response to the terpolymer poly(glu51lys34tyr15) (GLT). No response to GLT occurred when the APC were from E-nonexpressor strains 4R and 7R. When APC from E-expressor strains were used and alloreactivity against the incompatible E molecules was removed by BUdR + light treatment, 7R T cells responded to GLT presented by 9R APC, but 4R T cells failed to respond to GLT presented by 2R APC. However, 4R T cells mounted a proliferative response to GLT presented by fully allogeneic 5R or 9R APC. The latter response was completely abolished by the depletion of cells alloreactive against 2R and 5R or 2R and 9R. Since removal of alloreactivity against 5R plus 9R did not affect the response of 4R T cells to GLT presented by either 5R or 9R cells, we conclude that the 4R T cells generated in response to GLT cross-react with the additional incompatibility presented by 2R cells, that is, the Ek beta chain. In contrast, 7R T cells recognizing GLT presented by 9R APC do not cross-react with Ek beta. These results demonstrate that "blind spots" in the T cell repertoire produced by depletion of cells alloreactive against a single chain of a class II MHC molecule can render a strain nonresponsive to a synthetic polypeptide antigen, and that this nonresponsiveness corresponds to that attributed to the MHC-linked Ir genes.
Mortality of patients with COPD participating in chronic disease management programmes: a happy end?
Authors: I Peytremann-Bridevaux, P Taffe, B Burnand, P O Bridevaux, M A Puhan
Journal: Thorax (2014)

<h3>Background</h3> Concerns about increased mortality could question the role of COPD chronic disease management (CDM) programmes. We aimed at extending a recent Cochrane review to assess the effects of CDM on mortality in patients with COPD. <h3>Methods</h3> Mortality data were available for 25 out of 29 trials identified in a COPD integrated care systematic review. Meta-analysis using random-effects models was performed, followed by subgroup analyses according to study length (3–12 months vs &gt;12 months), main intervention component (exercise, self-management, structured follow-up) and use of an action plan. <h3>Results</h3> The meta-analysis showed no impact of CDM on mortality (pooled OR: 1.00, 95% CI 0.79 to 1.28). <h3>Conclusions</h3> These results do not suggest that CDM programmes expose patients with COPD to excessive mortality risk.
Thymic selection and cell division.
Authors: B Ernst, C D Surh, J Sprent
Journal: The Journal of Experimental Medicine (1995)

Cell division during thymic selection was studied with a system in which purified populations of T cell antigen receptor (TCR)- CD4+8+ (double-positive [DP]) cells and fetal thymic epithelial cells (TEC) were reaggregated in tissue culture. In this system, immature DP cells differentiate into mature single-positive (SP) CD4+8- and CD4-8+ TCRhi cells within 3-4 d, indicative of positive selection. By adding the DNA precursor, bromodeoxyuridine, to the cultures and staining cells for bromodeoxyuridine incorporation, T cell division in reaggregation cultures was found to be high on day 1, low on day 2, and high on days 4-5. Cell separation studies established that cell division on day 1 was restricted to DP blast cells. In the absence of blast cells, small DP cells failed to proliferate and differentiated into SP cells without cell division, thus indicating that proliferation is not an essential component of positive selection. This applied to SP cells generated within the first 2-3 d. Surprisingly, the SP cells generated later in culture showed a high rate of cell division; the proliferating SP cells were TCRhi and included both CD4+8- and CD4-8+ cells. Turnover of TCRhi SP cells was also prominent in the normal neonatal thymus and in TEC reaggregation cultures prepared with adult lymph node T cells. We speculate that division of mature SP cells in the perinatal thymic microenvironment is driven by stimulatory cytokines released from TEC. Such proliferation could be a device to expand the mature T cell repertoire before export to the periphery.
3D Cardiac Microtissues Encapsulated with the Co‐Culture of Cardiomyocytes and Cardiac Fibroblasts
Authors: Harpinder Saini, Ali Navaei, Alison Van Putten, Mehdi Nikkhah
Journal: Advanced Healthcare Materials (2015)

Cardiac tissue engineering has major applications in regenerative medicine, disease modeling and biological studies. Despite the significance, numerous questions still need to be explored to enhance the functionalities of engineered tissue substitutes. In this study, 3D cardiac microtissues are developed through encapsulation of cardiomyocytes and cardiac fibroblasts, as the main cellular constituents of native myocardium. The geometries of the constructs are precisely controlled and assessed for their role on synchronous contraction of the cells. Cardiomyocytes exhibit a native-like phenotype when co-cultured with cardiac fibroblasts as compared to the monoculture condition. Particularly, elongated F-actin fibers with abundance of sarcomeric α-actinin and troponin-I are observed within all layers of the constructs. Higher expressions of connexin-43 and integrin-β1 indicate improved cell-cell and cell-matrix interactions. Amongst co-culture conditions, 2:1 (cardiomyocytes: cardiac fibroblasts) ratio exhibits enhanced functionalities, whereas decreasing the construct size adversely affects the synchronous contraction of the cells. Overall, the study here indicates that the cell-cell ratio and the construct geometry are crucial parameters, which need to be optimized to enhance the functionalities of the engineered tissue substitutes.