tbuckley/cabot-search huggingface dataset:
Abstract P298: Association of Serum Sclerostin with Vascular Calcification in African Ancestry Men
Authors: Allison L Kuipers, Iva Miljkovic, J Jeffery Carr, James G Terry, Cara S Nestlerode, Yaorong Ge, Clareann H Bunker, Alan L Patrick, Joseph M Zmuda
Journal: Circulation (2015)

Objective: Sclerostin, a Wnt pathway antagonist, is an established regulator of bone mineralization in humans but its potential importance in the regulation of vascular calcification is less clear. Therefore, our objective was to assess the relationship of serum sclerostin levels with coronary and aortic artery calcification (CAC and AAC, respectively) in African ancestry men on the island of Tobago. Methods: Detailed health history, clinical exam and computed tomography scans of CAC and AAC were obtained in 191 men aged ≥40 years (mean(SD): 62.9(8.0)years) recruited without regard to health status. Fasting serum samples were drawn and stored at -80°C until time of assay. Serum sclerostin levels were measured using ELISA according to manufacturer’s protocol (Biomedica Gruppe, Vienna, Austria). Multivariable logistic regression models were used to assess the cross-sectional association of sclerostin with prevalent arterial calcification. Results: In unadjusted analyses, the 57 of 191 (29.8%) of men with CAC were older, more likely to be hypertensive, had lower kidney function and had greater serum sclerostin (all P-values&lt;0.05). The 131 of 191 (68.6%) of men with AAC were also older and more likely to be hypertensive, but they had greater total body fat and were more likely to be on statins, as well (all P-values&lt;0.05). Mean(SD) sclerostin was 45.2 pmol/l (15.6 pmol/l). After adjusting for risk factors including age, physical and lifestyle characteristics, comorbidities, lipoproteins and kidney function, 1 SD greater sclerostin level was associated with 1.61-times (95%CI 1.02-2.53) greater odds of having CAC. Sclerostin was not associated with AAC in any model. Conclusions: This is the first study to show that, among African ancestry men, greater serum sclerostin levels were associated with CAC. In addition to its known role in bone mineralization, the Wnt antagonist, sclerostin, may also play a role in calcification of the coronary arteries.
Matters Arising: Role of HLA genes in familial spondyloarthropathy
Authors: M A Brown, A. M. Crane, B. P. Wordsworth, R. Said-Nahal, C. Miceli-Richard, M. Breban
Journal: Annals of the Rheumatic Diseases (2002)

Said-Nahal and colleagues report an intriguing finding of an association with HLA-DR4 independent of B27 in families with ankylosing spondylitis (AS),1 a finding highlighted by an accompanying editorial.2 The approach of studying B27 positive and B27 negative haplotypes may prove powerful in identifying further cis or trans encoded genes involved in AS. However, the reported association of DR4 with AS is quite a surprising finding given that no difference was noted in B27-DR4 haplotype frequencies in patients and ethnically matched healthy controls. Many previous studies have not reported any such association,3–9 including a similar preliminary study by the same authors.10 Although these studies were mainly case-control studies, population stratification is highly unlikely to cause a false negative finding if the effect size of the reported association with DR4 is as high as Said-Nahal and colleagues describe...
The prevalence and impact of heavy menstrual bleeding among athletes and mass start runners of the 2015 London Marathon
Authors: Georgie Bruinvels, Richard Burden, Nicola Brown, Toby Richards, Charles Pedlar
Journal: British Journal of Sports Medicine (2015)

The single most common cause of iron deficiency anaemia in the developed world in premenopausal females is the menstrual cycle.1 It is well recognised and reported that amenorrhoea and oligomenorrhoea are common in elite athletes typically as a result of relative energy deficiency;2 however, little is known about the prevalence of other menstrual abnormalities. Heavy menstrual bleeding (HMB or menorrhagia ) affects a quarter of the general population,3 yet no data exist for athletes or exercising women. It is possible that HMB might impact significantly on women's participation in sport. HMB can lead to fatigue, anxiety, reduced mood and energy levels with a negative impact on quality of life and productivity.4 Furthermore, iron turnover in exercising females …
Principles of the new sex therapy
Authors: W H Master, V E Johnson
Journal: American Journal of Psychiatry (1976)

The authors review the development of their rapid treatment dual-sex therapy for sexual dysfunction. The basic tenets of the new sex therapy include 1) sound knowledge of physiology, endocrinology, and metabolic function, 2) institution of psychotherapy only when organic factors have been identified or ruled out, 3) treatment of the couple as a unit by dual-sex therapy teams, 4) a short-term intensive program, and 5) education in techniques of verbal and nonverbal communication. Since its inception in 1958, the new therapy has been adopted, modified, and examined by clinicians and researchers all over the world. The authors suggest that professionals interested in effective treatment for sexual dysfunction should improve techniques, train personnel, and encourage sound research.
Transfusion and Severe Anaemia
Authors: S V SUKHORUKIKH
Journal: BMJ (1965)

Leading Articles BRIRISH skeleton and in the unerupted teeth.The same investigators studied the effect of giving six normal premature babies 100 /%g./ml.tetracycline daily for 9-12 days.During this time the growth rate of the fibula in the children was depressed by 30 to 400/,, as compared with untreated controls.After treat- ment was stopped complete recovery took place after a tem- porary period of increased growth.The only report of the possible effect of tetracycline on the foetus when given in early pregnancy is in a letter to the B.M.7. by M. P. Carter and F. Wilson.8They described a baby who was born with absent ring and little fingers.The child's mother had had tetracycline (12 doses of 250 mg.) for acute bronchitis in early pregnancy when the age of the foetus was about 33 days.Hence tetracyclines administered during pregnancy pass through the placenta, are concentrated in the foetal skeleton, and may diminish skeletal growth.Though in view of their widespread use serious effects are probably few, there seems little doubt that (like some other chemotherapeutic agents)9 they should not be used to treat pregnant women unless they are specifically indicated for severe infection resistant to other less toxic drugs.
Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes
Authors: Kaifu Chen, Zhong Chen, Dayong Wu, Lili Zhang, Xueqiu Lin, Jianzhong Su, Benjamin Rodriguez, Yuanxin Xi, Zheng Xia, Xi Chen, Xiaobing Shi, Qianben Wang, Wei Li
Journal: Nature Genetics (2015)
Severe CAP: Can the CURB65 score and PT discriminate between ICU survivors and non-survivors?
Authors: Ricardo José, Mohammed Omar, James Goldring, Rachel Chambers, Jeremy Brown, Banwari Agarwal
Journal: European Respiratory Journal (2013)

Introduction: Community acquired pneumonia (CAP) is the most common cause of infectious disease related mortality world-wide. Predicting intensive care (ICU) mortality from severe CAP is important. Our aim was to assess the ability of the CURB65 score and prothrombin time (PT) to discriminate between survivors and non-survivors of CAP admitted to the ICU compared to other mortality prediction scores.

Methods: Retrospective review of adult patients with CAP admitted to our ICU between January 2006 and October 2011. CAP was defined as an ICU coding diagnosis of pneumonia and evidence of consolidation on a chest x-ray within 48 hours of hospital admission. Demographic, clinical, laboratory, and outcome data were collected from the ICU and pathology databases.

Results : 96 patients with CAP were identified. Patients had severe critical illness, and lung injury, with mean (SD) SAPS II score and lowest P/F ratio of 45 (14) and 132 (70) mmHg respectively on the day of ICU admission. ICU and hospital mortality were 38.5% and 42.7%. Receiver operating curve analysis (AUC) for disease severity scoring systems to predict ICU mortality are listed in Table 1.

Conclusion: : The CURB65 score at ICU admission has good ability to discriminate between ICU survivors and non-survivors. The sensitivity of this score may be improved by the addition of a point for prothrombin time >17 s.

View this table:

Receiver operating curve analysis (AUC) for severity of disease scoring systems to predict ICU mortality from CAP
Mechanisms regulating acidic extracellular pH induced lysosome trafficking in prostate cancer
Authors: Joshua Steffan, Tomas Welbourne, James Cardelli
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3097 

A low extracellular pH has been associated with tumor progression and increased invasive capacity (Rofstad, et al. Cancer Res 2006(13): 6699-707). This condition induces an outward movement of lysosomes and release of proteases; however, the mechanisms regulating lysosome trafficking under these conditions remain largely undefined. To address the mechanisms regulating lysosome outward movement, we used the DU-145 prostate cancer cell line as a model. We found that a low extracellular pH of 6.4-6.8 rapidly induced a peripheral lysosome redistribution that was dependent upon intact microtubules, since nocodazole inhibited outward movement. Immunofluorescence microscopy indicated that lysosomes were the only endocytic organelles that underwent peripheral redistribution. In addition, the PI3-Kinase pathway and members of the Rho GTPase family also played roles since LY294002 (a specific PI3K inhibitor) and C3-Transferase (a Rho family inhibitor) inhibited lysosome movement. The sodium-proton exchanger NHE-1 plays a role in regulating intracellular pH, thus to determine the role of NHE-1 in regulating lysosome redistribution, we used two different inhibitors. Treatment with Troglitazone (Tro; also an anti-diabetic agent), not only inhibited lysosome redistribution, but also induced the clustering of lysosomes near the microtubule-organizing center. Ethyl-isopropyl-amiloride, another NHE-1 inhibitor, prevented the low extracellular pH induced outward movement of lysosomes, but did not cause a clustering of lysosomes. Furthermore, we have determined that in addition to microtubules, the MAP-Kinase pathway was involved in Troglitazone’s clustering effect since treatment with UO126 (a MAPK inhibitor) prevented lysosome clustering. In addition, DNA transfection experiments demonstrated that Rab7 and its downstream effector, RILP, also played a role in Tro induced lysosome clustering. Thus, a better understanding of the mechanisms by which Tro reverses lysosome redistribution will lead to novel therapeutic targets to reduce protease secretion, resulting in a decrease in tumor invasion.
The influence of religious/spiritual well‐being on quality of life in dermatological disease
Authors: H.F. Unterrainer, M. Lukanz, M. Pilch, S. Scharf, M. Glawischnig‐Goschnik, N. Wutte, R. Fink‐Puches, E. Aberer
Journal: British Journal of Dermatology (2015)
Abstract 2857: Metastatic site and response to pembrolizumab (anti-PD1 antibody) in melanoma
Authors: Paul Camille Tumeh*, Michael Rosenblum*, Nathan Handley, Katy Tsai, Robert Rodriguez S. Rodriguez, Niharika Khurana, Christina Harview, Marko Spasic, Phillip J. Sanchez, Jeremy Chang, I. Peter Shintaku, Emma Taylor, Bartosz Chmielowski, Tristan Grogan, David A. Elashoff, Robert H. Pierce, Adil Daud
Journal: Cancer Research (2015)

Abstract Therapies that block the PD-1/PD-L1 axis have shown significant clinical activity in melanoma and other cancers. Recent evidence has shown that pre-existing CD8 T cells infiltrates at the invasive tumor margin of metastatic melanoma are associated with the presence of the PD-1/PD-L1 immune axis and may predict response to therapy. We examined the relationship between site of metastatic disease, local immune response, and treatment outcome in patients with advanced melanoma treated with pembrolizumab. We studied patients enrolled in the pembrolizumab Phase I clinical trial in the intention to treat (ITT, N = 112) and full analysis set (FAS) cohorts (N = 96). Using quantitative immunohistochemistry and multi-parameter flow cytometry we analyzed the local immune response in pre-treatment metastatic samples according to organ site of metastasis and treatment outcome. The overall response rate was 40% with a median progression-free survival (PFS) of 5.58 months. The presence of melanoma metastatic to the liver (liver metastasis group) had an objective response rate (ORR) of 16% and median PFS of 2.79 months. The presence of melanoma metastatic to the lung (lung metastasis group) had an ORR of 64% and median PFS of 14.48 months. Preliminary analysis of samples obtained from patients with liver metastases showed reduced tumor infiltrating CD8+ T cells (TILs), PD-1 expression, and tumor PD-L1 expression in distant metastases. Phenotypic and functional analysis of TILs showed reduced percentages of partially exhausted PD-1+CTLA-4+CD8+ cells, which correlated with progression and with liver metastasis. These cells were shown to make IFNγ but not TNF or IL-2. Additionally, the presence of liver metastasis in melanoma patients prior to starting anti-PD1 therapy correlated with treatment failure. Liver metastasis was associated with fewer PD-1+ CTLA-4+ TILs in distant tumors. These preliminary results warrant further investigation into determining whether site of metastasis modulates the systemic immune response to PD-1/PD-L1 blocking therapies. Citation Format: Paul Camille Tumeh*, Michael Rosenblum*, Nathan Handley, Katy Tsai, Robert Rodriguez S. Rodriguez, Niharika Khurana, Christina Harview, Marko Spasic, Phillip J. Sanchez, Jeremy Chang, I. Peter Shintaku, Emma Taylor, Bartosz Chmielowski, Tristan Grogan, David A. Elashoff, Robert H. Pierce, Adil Daud. Metastatic site and response to pembrolizumab (anti-PD1 antibody) in melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2857. doi:10.1158/1538-7445.AM2015-2857
Critical link between glycogen synthase kinase 3β and forkhead box P3 in patients with chronic rhinosinusitis with nasal polyps
Authors: Xingmei Wu, Sihua Wang, Miaomiao Han, Bin Song, Ping Ye, Shanshan Ma, Jun Li, Fenghong Chen, Geng Xu, Qingqing Ding, Jiahong Xia, Huabin Li
Journal: Journal of Allergy and Clinical Immunology (2015)
AZD6244 (ARRY-142886) versus capecitabine (CAP) in patients (pts) with metastatic colorectal cancer (mCRC) who have failed prior chemotherapy
Authors: I. Lang, A. Adenis, K. Boer, P. Escudero, T. Kim, M. Valladares, N. Sanders, G. Pover, J. Douillard
Journal: Journal of Clinical Oncology (2008)

4114 Background: There is a strong correlation between human cancers and constitutive activation of the Raf/MEK/ERK signaling pathway. AZD6244, a potent, selective, ATP uncompetitive inhibitor of MEK1/2 has shown anti-tumor activity as monotherapy in several tumor models, including human colorectal tumors. This study aimed to compare the efficacy and safety of AZD6244 with that of CAP in pts with mCRC who had failed prior irinotecan and/or oxaliplatin therapy, where no standard of care exists. Methods: In this Phase II exploratory multicenter, open, two-arm parallel-group study, pts with histologically confirmed mCRC who had failed one or two previous oxaliplatin and/or irinotecan regimens were randomized 1:1 to either AZD6244 (100 mg BID) or CAP (1,250 mg/m2 BID) until objective and/or clinical progression. Eligibility included pts with a WHO performance status of 0–2 and life expectancy of >12 weeks. The primary objective was to assess the efficacy of AZD6244 vs CAP for the treatment of mCRC by assessment of disease progression. Results: A total of 69 pts (aged 38–81 years; 75% third-line) were randomized to AZD6244 (34) or CAP (35). The two groups were comparable for baseline characteristics. There was no significant difference between AZD6244 and CAP in the number of pts with a progression event: 28 pts (82%) vs 28 pts (80%), respectively (HR 1.08; 80% CI 0.73, 1.58; p = 0.80). This primary analysis was supported by a secondary analysis of PFS (AZD6244: median 81 days; CAP: median 88 days; HR 1.08; 80% CI 0.76, 1.52; p = 0.78). Most pts (97%) in both treatment arms experienced adverse events (AEs). The most common AEs with AZD6244 were dermatitis acneiform (56%), diarrhea (44%), asthenia (29%), and edema peripheral (26%). The most common AEs with CAP were palmar plantar erythrodysesthesia syndrome (56%), diarrhea (26%), nausea (26%), and asthenia (26%). Each group experienced 11 serious AEs (6 pts in each group), but no two pts experienced the same event. Conclusions: No statistically significant difference was observed between AZD6244 and CAP in the number of pts with a disease progression event. AZD6244 was well tolerated in this patient population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Novartis AstraZeneca Amgen, AstraZeneca, Novartis Pfizer, sanofi-aventis
MRC SORCE trial: Analysis of patients' presenting characteristics, tumor staging, and surgical approach.
Authors: Alastair W. S. Ritchie, Angela M. Meade, Louise Choo, Ben Smith, Andrew Welland, Adam Gregory, Richard S. Kaplan, Tim Eisen
Journal: Journal of Clinical Oncology (2014)

496 Background: SORCE is a randomised double blind trial of sorafenib, given for one or three years, versus placebo for patients at moderate or high risk of disease recurrence after surgical excision of primary renal cell carcinoma (RCC). Methods: Between July 2007 and April 2013, 1,711 patients were recruited from the UK (78%), Australia, France, Belgium, Denmark, The Netherlands and Spain. We describe the presenting characteristics, staging and surgical details of the randomised population. The surgical approach was at the surgeon’s discretion. Results: Baseline information is available for 1,681 patients (98%). Median age was 59 years (range 19 to 86): 1,195 (71%) were male. Histology was conventional/clear cell in 86%. T category was pT1a (&lt;1%), pT1b (11%), pT2 (23%), pT3a-4 (65%). 47% were at high risk of recurrence with Leibovich scores of ≥6. Surgical data are available for 1,528 patients (89%). Total (radical) nephrectomy was performed for 97% of patients with 44% having laparoscopic surgery, of which 60% had a transperitoneal approach and 10% required conversion to open surgery. Some form of lymph node dissection was performed in 25% of patients (33% of open procedures and 15% of lap. procedures). The ipsi-lateral adrenal was removed in 47% and 11% had simultaneous resection of other structures/organs. Excision of venous extension was required in 19%. Laparoscopic procedures were performed for 58% of patients with maximum tumour diameter (MTD) &lt;10cm and 17% of those with MTD ≥ 10 cm. Intra-operative complications were reported in 6% and post-operative complications reported in 12%. Hospital stay was median (IQR) 4 days (3-5) for patients having laparoscopic procedures and 7 days (5-8) for open surgery. Hospital stay was median (IQR) 8 days (6-11) for those having post-operative complications compared to 5 days (4-7) for uncomplicated recovery. Conclusions: These data reveal the varied surgical approaches to excision of primary RCC and will inform future adjuvant trials. The use of lymph node dissection appears arbitrary and evidence of benefit from randomised controlled trials is required. Analysis of the effect of sorafenib on disease free survival is likely to be performed in 2016. Clinical trial information: ISRCTN38934710.
Terminal Ileum Endometriosis Causing Intestinal Obstruction: A Case Report and Review of Literature
Authors: P.S. Te, W. Alba, D. Ang
Journal: Clinical Gastroenterology and Hepatology (2015)

Endometriosis affects 10% of females within reproductive age. The intestine is affected in 3% of those with ectopic endometriosis, and the terminal ileum is rarely affected. The most common presentation is bleeding and seldom presents as acute bowel obstruction.
Making Sense of Variations in Prevalence Estimates of Depression in Cancer: A Co-Calibration of Commonly Used Depression Scales Using Rasch Analysis
Authors: Sylvie D. Lambert, Kerrie Clover, Julie F. Pallant, Benjamin Britton, Madeleine T. King, Alex J. Mitchell, Gregory Carter
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: The use of different depression self-report scales warrants co-calibration studies to establish relationships between scores from 2 or more scales. The goal of this study was to examine variations in measurement across 5 commonly used scales to measure depression among patients with cancer: Hospital Anxiety and Depression Scale-Depression subscale (HADS-D), Centre for Epidemiologic Studies Depression Scale (CES-D), Patient Health Questionnaire-9 (PHQ-9), Beck Depression Inventory-II (BDI-II), and Depression Anxiety and Stress Scale-Depression subscale (DASS-D). Methods: The depression scales were completed by 162 patients with cancer. Participants were also assessed by the major depressive episode module of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Rasch analysis and receiver operating characteristic curves were performed. Results: Rasch analysis of the 5 scales indicated that these all measured depression. The HADS and BDI-II had the widest measurement range, whereas the DASS-D had the narrowest range. Co-calibration revealed that the cutoff scores across the scales were not equivalent. The mild cutoff score on the PHQ-9 was easier to meet than the mild cutoff score on the CES-D, BDI-II, and DASS-D. The HADS-D possible cutoff score was equivalent to cutoff scores for major to severe depression on the other scales. Optimal cutoff scores for clinical assessment of depression were in the mild to moderate depression range for most scales. Conclusions: The labels of depression associated with the different scales are not equivalent. Most markedly, the HADS-D possible case cutoff score represents a much higher level of depression than equivalent scores on other scales. Therefore, use of different scales will lead to different estimates of prevalence of depression when used in the same sample.