tbuckley/cabot-search huggingface dataset:
The endometrium in stimulated cycles for IVF
Authors: Claire Bourgain, Paul Devroey
Journal: Human Reproduction Update (2003)

Ovarian stimulation for IVF is known to affect luteal phase function. The endometrium in IVF cycles is thus subject to an altered endocrinological environment and to a possible direct effect of the ovarian stimulation therapy. Factors influencing the endometrial receptivity in such cycles are poorly understood. Studies comparing the endometrium in IVF cycles with natural cycles as controls have shown premature secretory changes in the post‐ovulatory and early luteal phase of IVF cycles, followed by a large proportion of dyssynchronous glandular and stromal differentiation in the mid‐luteal phase. These findings suggest a profound modification of luteal endometrial development in stimulated cycles. This hypothesis is further supported by the demonstration of a modified endometrial steroid receptor regulation and a profound antiproliferative effect in IVF cycles. The time of maximal endometrial receptivity is defined as the implantation window and is characterized by the expression of various endometrial products, among which pinopodes, integrins and leukaemia inhibitory factor are best described. Premature expression of pinopodes and integrins are in line with the observation of precocious luteal transformation following ovarian stimulation, although the clinical relevance with respect to the establishment of a clinical pregnancy awaits further validation. Studies exploring the endometrium within the cycle of embryo transfer have shown a deleterious effect of severe peri‐ovulatory maturation advancement exceeding 3 days, as no clinical pregnancies were obtained in this condition. Further unravelling of molecules involved in the implantation mechanism is needed for a better comprehension of the link between altered endometrial development and receptivity in IVF cycles.
Avian Flu to Human Influenza
Authors: David B. Lewis
Journal: Annual Review of Medicine (2006)

Influenza A viral infection causes substantial annual morbidity and mortality worldwide, particularly for infants, the elderly, and the immunocompromised. The virus mainly replicates in the respiratory tract and is spread by respiratory secretions. A growing concern is the recent identification of H5N1 strains of avian influenza A in Asia that were previously thought to infect only wild birds and poultry, but have now infected humans, cats, pigs, and other mammals, often with fatal results, in an ongoing outbreak. A human pandemic with H5N1 virus could potentially be catastrophic because most human populations have negligible antibody-mediated immunity to the H5 surface protein and this viral subtype is highly virulent. Whether an H5N1 influenza pandemic will occur is likely to hinge on whether the viral strains involved in the current outbreak acquire additional mutations that facilitate efficient human-to-human transfer of infection. Although there is no historical precedent for an H5N1 avian strain causing widespread human-to-human transmission, some type of influenza A pandemic is very likely in the near future. The possibility of an H5N1 influenza pandemic has highlighted the many current limitations of treatment with antiviral agents and of vaccine production and immunogenicity. Future vaccine strategies that may include more robust induction of T-cell responses, such as cytotoxic T lymphocytes, may provide better protection than is offered by current vaccines, which rely solely or mainly on antibody neutralization of infection.
P199 Merseyside &amp; Cheshire Cancer Network (MCCN) Audit: Survival Analysis of Lung Cancer Patients with a Performance Status of 3 (PS3) Based Upon the Reason For Their Poor Performance Status and Whether or Not They Had a Tissue Diagnosis
Authors: P Owen, J Hendry
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> Lung Cancer patients with a PS3 often fall on the boundary between fitness for active oncological treatments and “best supportive care”. Some patients with PS3 are deteriorating rapidly because of advanced cancer symptoms and have a very poor prognosis. Others have stable chronic health problems that influence PS. <h3>Aims</h3> -To determine the percentage of patients with PS3 who fall into these subcategories and compare 12 month survival -To ask whether having a tissue diagnosis in patients with PS3 improves outcome. Assigning a PS3 to a patient may influence whether or not a tissue diagnosis is pursued. In some cases this may be because the patient has severe cardiorespiratory disease and a biopsy is unsafe. In other cases, the multidisciplinary team may decide that the patient is not fit to have active oncological treatment so pursuing a biopsy would not alter management, and might even be unethical because of the risk incurred. <h3>Methods</h3> All lung cancer units in MCCN were asked to complete a questionnaire for 50 consecutive Lung Cancer patients with PS3 (most were diagnosed in 2010), which was then compared with death data from the North West Cancer Intelligence Service. <h3>Results</h3> Survival is generally greater in patients who are given a PS3 because they are stable due to chronic illness (34.5% were alive after 12 months) and poorer in those deteriorating due to advanced cancer symptoms (4.1%) or a combination of the two (13.1%). In neither patients with PS3 because of ill health, nor patients with PS3 because of advanced cancer symptoms was there a clear survival advantage for patients who had a tissue diagnosis of cancer as opposed to a clinical and radiological diagnosis. <h3>Conclusions</h3> Based on this data, there is no explicit survival advantage in pursuing tissue diagnosis in patients with PS3. In our network, those patients with PS3 who are fit for active oncological treatment received it even when it was considered inappropriate to pursue histology. In the future, should targeted therapies become available that can be tolerated in patients with PS3, the case for pursuit of histology will be stronger.
Arterial Stiffness Increases With Deteriorating Glucose Tolerance Status
Authors: Ronald M.A. Henry, Piet J. Kostense, Annemieke M.W. Spijkerman, Jacqueline M. Dekker, Giel Nijpels, Robert J. Heine, Otto Kamp, Nico Westerhof, Lex M. Bouter, Coen D.A. Stehouwer
Journal: Circulation (2003)

Background— Type 2 diabetes (DM-2) and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease risk. In nondiabetic individuals, increased arterial stiffness is an important cause of cardiovascular disease. Associations between DM-2 and IGM and arterial stiffness have not been systematically investigated. Methods and Results— In a population-based cohort (n=747; 278 with normal glucose metabolism, 168 with IGM, and 301 with DM-2; mean age, 68.5 years), arterial stiffness was ultrasonically estimated by distensibility and compliance of the carotid, femoral, and brachial arteries and by the carotid elastic modulus. After adjustment for age, sex, and mean arterial pressure, DM-2 was associated with increased carotid, femoral, and brachial stiffness, whereas IGM was associated only with increased femoral and brachial stiffness. Carotid but not femoral or brachial stiffness increased from IGM to DM-2. Standardized βs (95% CI) for IGM and DM-2, compared with normal glucose metabolism, were −0.06 (−0.23 to 0.10) and −0.37 (−0.51 to −0.23) for carotid distensibility; −0.02 (−0.18 to 0.18) and −0.25 (−0.40 to −0.09) for carotid compliance; −0.05 (−0.23 to 0.13) and 0.25 (0.10 to 0.40) for carotid elastic modulus; −0.70 (−0.89 to −0.51) and −0.67 (−0.83 to −0.52) for femoral distensibility; and −0.62 (−0.80 to −0.44) and −0.79 (−0.94 to −0.63) for femoral compliance. The brachial artery followed a pattern similar to that of the femoral artery. Increases in stiffness indices were explained by decreases in distension, increases in pulse pressure, an increase in carotid intima-media thickness, and, for the femoral artery, a decrease in diameter. Hyperglycemia or hyperinsulinemia explained only 30% of the arterial changes associated with glucose tolerance. Adjustment for conventional cardiovascular risk factors did not affect these findings. Conclusions— IGM and DM-2 are associated with increased arterial stiffness. An important part of the increased stiffness occurs before the onset of DM-2 and is explained neither by conventional cardiovascular risk factors nor by hyperglycemia or hyperinsulinemia.
Phase II Study of Ecteinascidin-743 in Advanced Pretreated Soft Tissue Sarcoma Patients
Authors: A. Yovine, M. Riofrio, J.Y. Blay, E. Brain, J. Alexandre, C. Kahatt, A. Taamma, J. Jimeno, C. Martin, Y. Salhi, E. Cvitkovic, J.L. Misset
Journal: Journal of Clinical Oncology (2004)

Purpose A multicenter phase II study evaluating efficacy, safety, and pharmacokinetics of ecteinascidin-743 (ET-743) in pretreated advanced soft tissue sarcoma patients. Patients and Methods Patients received ET-743 1,500 μg/m 2 (24-hour intravenous infusion) every 3 weeks (group 1, 26 patients with one to two prior single agents or one previous combination chemotherapy; group 2, 28 patients with three or more prior single agents or two or more previous combination chemotherapies). Results Patients (30 women, 24 men) had a median age of 48 years (range, 22 to 71 years); 41% had leiomyosarcoma (eight of 22 of uterine origin), a median of two involved organs (range, one to four), and 93% had documented progressive disease at study entry. Patients received a median of three cycles (range, one to 20); 28% received six or more cycles. Fifty-two patients were assessable for response (WHO criteria): two partial responses, four minor responses, and nine with stable disease (≥ 6 months). Three patients were rendered tumor free after surgery. Median progression-free survival was 1.9 months (range, 0.69 to 17.90 months); 24% of patients were progression free at 6 months. Median survival was 12.8 months, with 30% of patients alive at 2 years. Four patients withdrew because of treatment-related toxicity. Two treatment-related deaths occurred (renal failure and febrile neutropenia, and rhabdomyolysis and decompensated cirrhosis, respectively) that were probably related to protocol eligibility violations. Reversible grade 3 to 4 AST or ALT occurred in 50% of patients and grade 3 to 4 neutropenia occurred in 61% of patients, with six episodes of febrile neutropenia. Nausea, vomiting, and asthenia were prevalent but mild and manageable. Conclusion With a 4% overall response rate (95% CI, 0.5 to 12.8) and an 11% rate of third-party-verified tumor regression (overall response rate + minor response), ET-743 has a 24% 6-month disease progression control rate, confirming evidence of antitumoral activity and a manageable safety profile in patients experiencing disease progression with pretreated soft tissue sarcoma.
Abstract 3840: Evaluation of the synergetic effect of a combination of dehydroxymethylepoxyquinomicin and gemcitabine on liver metastasis of pancreatic cancer
Authors: Keiichi Suzuki, Osamu Takeuchi, Asako Takizawa, Kazuo Umezawa, Yuko Kitagawa
Journal: Cancer Research (2012)

Abstract Activation of the nuclear transcription factor-kappaB (NF-κB) has been implicated in the progression and metastasis of pancreatic cancer. This study was designed to evaluate the effects of a novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) in inhibition of liver metastasis of pancreatic cancer in a clinical liver metastasis-mimicking mouse model in which cancer cells were intra-portal injected under small laparotomy. Moreover, the synergistic effect of combination therapy with DHMEQ and gemcitabine (GEM) was investigated. Cytotoxicity of DHMEQ and GEM was evaluated by cell growth inhibition assay. Both DHMEQ and GEM monotherapies inhibited cell growth of the human pancreas cell line AsPC-1. However, there was no synergistic effect in the combination therapy. For the in vivo study, male BALB/c nude mice were xenografted with intra-portal vein injection of AsPC-1. Mice were divided into four groups: 1) control (without any treatment), 2) GEM-treated group, 3) DHMEQ-treated group, and 4) combined treatment group (GEM+DHMEQ). Mice were fed for four weeks, and the number of liver metastases, induction of apoptosis in metastasis focuses and angiogenesis were investigated after sacrifice. The number of liver metastasis was decreased significantly in GEM group, DHMEQ group and GEM+DHMEQ group compared with control group. Significant inductions of apoptosis were revealed in GEM group and DHMEQ group compared with control group, in which apoptosis bodies in metastasis sections were counted by using the TUNEL method. Moreover, combination therapy of DHMEQ+GEM resulted in the strongest inductions of apoptosis. Tumor vessels were identified by immunohistochemical staining of tumor metastasis sections with an antibody against CD31. There was a large reduction in the number of CD31-positive vessels in the tumor of DHMEQ or/and GEM-treated mice as compared with control group. However, there was an inconsistency in the results of cell growth inhibition assay (in vitro) and mice metastasis model (in vivo). Thus we evaluated effect of combination therapy in the invasive potential of tumor cells by using chemoinvasion assay. The invasion ability was significantly inhibited in the GEM group, DHMEQ group and GEM+DHMEQ group. Furthermore, real-time PCR was performed to evaluate expression of mRNA of MMP-9. The expression levels of MMP-9 were inhibited in respective groups in the same order. In conclusion, the anti-tumor effects of combination therapy were significant, as evidenced by angiogenesis inhibition, apoptosis induction and invasiveness inhibition rather than cell growth inhibition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3840. doi:1538-7445.AM2012-3840
Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice
Authors: Som G. Nanjappa, Jane H. Walent, Michel Morre, M. Suresh
Journal: Journal of Clinical Investigation (2008)

IL-7 is integral to the generation and maintenance of CD8(+) T cell memory, and insufficient IL-7 is believed to limit survival and the persistence of memory CD8(+) T cells. Here, we show that during the mouse T cell response to lymphocytic choriomeningitis virus, IL-7 enhanced the number of memory CD8(+) T cells when its administration was restricted to the contraction phase of the response. Likewise, IL-7 administration during the contraction phase of the mouse T cell response to vaccinia virus or a DNA vaccine potentiated antigen-specific CD8(+) memory T cell proliferation and function. Qualitatively, CD8(+) T cells from IL-7-treated mice exhibited superior recall responses and improved viral control. IL-7 treatment during the memory phase stimulated a marked increase in the number of memory CD8(+) T cells, but the effects were transient. IL-7 therapy during contraction of the secondary CD8(+) T cell response also expanded the pool of memory CD8(+) T cells. Collectively, our studies show differential effects of IL-7 on memory CD8(+) T cell homeostasis and underscore the importance of the timing of IL-7 therapy to effectively improve CD8(+) T cell memory and protective immunity. These findings may have implications in the clinical use of IL-7 as an immunotherapeutic agent to bolster vaccine-induced CD8(+) T cell memory.
Prevalence and reservoirs of A. xylosoxidans and S. maltophilia in cystic fibrosis center
Authors: Irina Asherova, Svetlana Monachova, Marina Ershova, Svetlana Angelova
Journal: European Respiratory Journal (2011)

A. xylosoxidans (AX)  and  S. maltophilia  (SM)  becomes more and more important pathogens of lung disease in CF patients. Little is known about the routes of transmission of these pathogens from environmental or hospital sources to the patients. We hypothesised that strains of  AX  and  SM  are nosocomially acquired by CF patients.   Methods:  259 sputum samples, cough swabs were taken from 38 patients attending the Regional CF Center in 2010. Bacterial isolates were obtained from the hospital environment (sinks, toilets, physiotherapy equipments, nebulizers), personnel hands.   Results:  Four (10,5%) of patients were colonised by  AX . According to the European consensus criteria two of them were chronicaly infected and had an accelerating loss of lung function. In six patients (15,8%)  SM  was detected. Their clinical condition was stable. Two patients (siblings) were chronically colonized with  SM . In 8 cases (80%) bacterial pathogens were detected after i.v. anti-pseudomonal therapy and hospitalisation.  AX  and  SM  were isolated from the sinks of a mixed infectious disease ward (32,0% and 66,7% respectively. 40% of toilets were contaminated with  AX  and  SM  strains. All inhalation systems and personnel hand cultures were  AX  and  SM  negative. One  SM  strain was isolated from the vest for high frequency chest wall oscillation and one  SM  strain from the physiotherapist hands at the end of the working day. Similar antibiotics sensitivity suggested a possible trasmission route from the hospital environment and personnel hands to the patients.   Conclusion:  The role of these microorganisms can be underestimated. Improved hygienic measures in CF centers are required to prevent risk of bacterial transmission.
Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque psoriasis
Authors: M G Lebwohl, D L Breneman, B S Goffe, J R Grossman, M R Ling, J Milbauer, S H Pincus, R G Sibbald, L J Swinyer, G D Weinstein, D A Lew-Kaya, J C Lue, J R Gibson, J Sefton
Journal: Journal of the American Academy of Dermatology (1998)
Use of the Estimated Glucose Disposal Rate as a Measure of Insulin Resistance in an Urban Multiethnic Population With Type 1 Diabetes
Authors: Eric J. Epstein, Jamie L. Osman, Hillel W. Cohen, Swapnil N. Rajpathak, Oksana Lewis, Jill P. Crandall
Journal: Diabetes Care (2013)

OBJECTIVE Insulin resistance has been described in type 1 diabetes mellitus, is related to risk of vascular complications, and may be more common in certain ethnic groups. Estimated glucose disposal rate (eGDR) is a validated clinical tool for estimating insulin sensitivity in type 1 diabetes. Because previous reports of eGDR in adults with type 1 diabetes have included few ethnic minorities, this study explored interethnic differences in eGDR and the relationship of eGDR with diabetic vascular complications. RESEARCH DESIGN AND METHODS We conducted a cross-sectional study using a sample that included 207 white, black, or Hispanic adults with prior clinical diagnosis of type 1 diabetes who were receiving care at an urban academic medical center. eGDR (milligrams per kilogram per minute) was calculated using HbA1c, waist circumference, and hypertensive status. Race/ethnicity was self-reported. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% CIs of association of eGDR with diabetes complications (cardiovascular disease, retinopathy, albuminuria, and chronic kidney disease above stage 3). RESULTS Forty-two percent of the participants were women, and mean age was 45 ± 15 years; 34% were white, 32% were Hispanic, and 34% were black. Ethnicity was significantly associated with eGDR; blacks had significantly lower eGDR (5.66 ± 2.34) than Hispanics (6.70 ± 2.29) and whites (7.20 ± 2.03) (P &amp;lt; 0.001). Patients with the lowest eGDR compared with the highest had a significantly greater risk of any diabetes complication (OR 3.1 [95% CI 1.2–8.1]) compared with the least insulin-resistant patients. CONCLUSIONS In an urban clinic population of patients with type 1 diabetes, blacks were significantly less insulin sensitive than whites or Hispanics, and lower eGDR was associated with diabetes complications. Further study is needed to determine whether using eGDR to target interventions can improve outcomes.
Obesity, waist size and prevalence of current asthma in the California Teachers Study cohort
Authors: J Von Behren, M Lipsett, P L Horn-Ross, R J Delfino, F Gilliland, R McConnell, L Bernstein, C A Clarke, P Reynolds
Journal: Thorax (2009)

<h3>Background:</h3> Obesity is a risk factor for asthma, particularly in women, but few cohort studies have evaluated abdominal obesity which reflects metabolic differences in visceral fat known to influence systemic inflammation. A study was undertaken to examine the relationship between the prevalence of asthma and measures of abdominal obesity and adult weight gain in addition to body mass index (BMI) in a large cohort of female teachers. <h3>Methods:</h3> Prevalence odds ratios (ORs) for current asthma were calculated using multivariable linear modelling, adjusting for age, smoking and race/ethnicity. <h3>Results:</h3> Of the 88 304 women in the analyses, 13% (n = 11 500) were obese (BMI ⩾30 kg/m<sup>2</sup>) at baseline; 1334 were extremely obese (BMI ⩾40 kg/m<sup>2</sup>). Compared with those of normal weight, the adjusted OR for adult-onset asthma increased from 1.40 (95% confidence interval (CI) 1.31 to 1.49) for overweight women to 3.30 (95% CI 2.85 to 3.82) for extremely obese women. Large waist circumference (&gt;88 cm) was associated with increased asthma prevalence, even among women with a normal BMI (OR 1.37, 95% CI 1.18 to 1.59). Among obese women the OR for asthma was greater in those who were also abdominally obese than in women whose waist was ⩽88 cm (2.36 vs 1.57). Obese and overweight women were at greater risk of severe asthma episodes, measured by urgent medical visits and hospital admissions. <h3>Conclusions:</h3> This study confirms the association between excess weight and asthma severity and prevalence, and showed that a large waist was associated with increased asthma prevalence even among women considered to have normal body weight.
Divergence Times in Caenorhabditis and Drosophila Inferred from Direct Estimates of the Neutral Mutation Rate
Authors: A. D. Cutter
Journal: Molecular Biology and Evolution (2008)

Accurate inference of the dates of common ancestry among species forms a central problem in understanding the evolutionary history of organisms. Molecular estimates of divergence time rely on the molecular evolutionary prediction that neutral mutations and substitutions occur at the same constant rate in genomes of related species. This underlies the notion of a molecular clock. Most implementations of this idea depend on paleontological calibration to infer dates of common ancestry, but taxa with poor fossil records must rely on external, potentially inappropriate, calibration with distantly related species. The classic biological models Caenorhabditis and Drosophila are examples of such problem taxa. Here, I illustrate internal calibration in these groups with direct estimates of the mutation rate from contemporary populations that are corrected for interfering effects of selection on the assumption of neutrality of substitutions. Divergence times are inferred among 6 species each of Caenorhabditis and Drosophila, based on thousands of orthologous groups of genes. I propose that the 2 closest known species of Caenorhabditis shared a common ancestor <24 MYA (Caenorhabditis briggsae and Caenorhabditis sp. 5) and that Caenorhabditis elegans diverged from its closest known relatives <30 MYA, assuming that these species pass through at least 6 generations per year; these estimates are much more recent than reported previously with molecular clock calibrations from non-nematode phyla. Dates inferred for the common ancestor of Drosophila melanogaster and Drosophila simulans are roughly concordant with previous studies. These revised dates have important implications for rates of genome evolution and the origin of self-fertilization in Caenorhabditis.