tbuckley/cabot-search huggingface dataset:
New Definition for the Partial Remission Period in Children and Adolescents With Type 1 Diabetes
Authors: Henrik B. Mortensen, Philip Hougaard, Peter Swift, Lars Hansen, Reinhard W. Holl, Hilary Hoey, Hilde Bjoerndalen, Carine de Beaufort, Francesco Chiarelli, Thomas Danne, Eugen J. Schoenle, Jan Åman
Journal: Diabetes Care (2009)

OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS A total of 275 patients aged &amp;lt;16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual β-cell function. RESULTS By multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient −0.21, P &amp;lt; 0.001) and insulin dose (−0.94, P &amp;lt; 0.001) was shown. These results suggested the definition of an insulin dose–adjusted A1C (IDAA1C) as A1C (percent) + [4 × insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C ≤9 corresponding to a predicted stimulated C-peptide &amp;gt;300 pmol/l was used to define partial remission. The IDAA1C ≤9 had a significantly higher agreement (P &amp;lt; 0.001) with residual β-cell function than use of a definition of A1C ≤7.5%. Between 6 and 12 months after diagnosis, for IDAA1C ≤9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C ≤7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose ≤0.5 units · kg−1 · 24 h−1 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (&amp;gt;300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months. CONCLUSIONS A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual β-cell function and has better stability compared with the conventional definitions.
Sweat tests to diagnose cystic fibrosis in adults.
Authors: G Lynch
Journal: BMJ (1983)

<h3>Abstract</h3> <h3>Introduction</h3> Racial and ethnic disparities in COVID-19 related infections, hospitalizations, and deaths have been well-documented. However, little research has examined racial and ethnic disparities in COVID-19 prevalence, determinants, and impacts among pregnant women. Within the United States, New Jersey was an early epicenter of the pandemic and experienced high rates of disease in the fall of 2020. <h3>Methods</h3> This study uses data from two New Jersey hospitals, which implemented universal testing of COVID-19 of pregnant women admitted for labor and delivery starting in March 2020. We will estimate prevalence of COVID-19 between March 2020 and November 2020 and compare prevalence rates across race and ethnicity. We will conduct multivariable logistic regression analysis to examine the associations of COVID-19 infection with patient demographic and health status predictors. We will also use multivariable linear and logistic regressions to examine the impact of COVID-19 symptomatic and asymptomatic infection on maternal and infant birth outcomes. <h3>Discussion</h3> This study will generate important policy implications on birth equity in the time of COVID-19 and guide future research studies related to COVID-19 in pregnant women. Results of this study will help to guide interventions and policies to center safe, accessible, and equitable maternity care within the strategic response to the pandemic.
IMPROVED EARLY DIAGNOSIS OF ADULT POLYCYSTIC KIDNEY DISEASE WITH FLANKING DNA MARKERS
Authors: M.H. Breuning, H. Brunner, J.J. Saris, G.J.B. Van Ommen, S.T. Reeders, J.W. Ijdo, A. Verwest, P.L. Pearson
Journal: The Lancet (1987)
Randomized, Controlled Trial of Cyclophosphamide, Methotrexate, and Fluorouracil Versus Cyclophosphamide, Doxorubicin, and Fluorouracil With and Without Tamoxifen for High-Risk, Node-Negative Breast Cancer: Treatment Results of Intergroup Protocol INT-0102
Authors: Laura F. Hutchins, Stephanie J. Green, Peter M. Ravdin, Danika Lew, Silvana Martino, Martin Abeloff, Alan P. Lyss, Craig Allred, Saul E. Rivkin, C. Kent Osborne
Journal: Journal of Clinical Oncology (2005)

We evaluated the efficacy of cyclophosphamide, methotrexate, and fluorouracil (CMF) versus cyclophosphamide, doxorubicin, and fluorouracil (CAF) in node-negative breast cancer patients with and without tamoxifen (TAM), overall and by hormone receptor (HR) status.Node-negative patients identified by tumor size (> 2 cm), negative HR, or high S-phase fraction (n = 2,690) were randomly assigned to CMF, CAF, CMF + TAM (CMFT), or CAF + TAM (CAFT). Cox regression evaluated overall survival (OS) and disease-free survival (DFS) for CAF versus CMF and TAM versus no TAM separately. Two-sided CIs and one-sided P values for planned comparisons were calculated.Ten-year estimates indicated that CAF was not significantly better than CMF (P = .13) for the primary outcome of DFS (77% v 75%; HR = 1.09; 95% CI, 0.94 to 1.27). CAF had slightly better OS than CMF (85% v 82%, HR = 1.19 for CMF v CAF; 95% CI, 0.99 to 1.43); values were statistically significant in the planned one-sided test (P = .03). Toxicity was greater with CAF and did not increase with TAM. Overall, TAM had no benefit (DFS, P = .16; OS, P = .37), but the TAM effect differed by HR groups. For HR-positive patients, TAM was beneficial (DFS, HR = 1.32 for no TAM v TAM; 95% CI, 1.09 to 1.61; P = .003; OS, HR = 1.26; 95% CI, 0.99 to 1.61; P = .03), but not for HR-negative patients (DFS, HR = 0.81 for no TAM v TAM; 95% CI, 0.64 to 1.03; OS, HR = 0.79; 95% CI, 0.60 to 1.05).CAF did not improve DFS compared with CMF; there was a slight effect on OS. Given greater toxicity, we cannot conclude CAF to be superior to CMF. TAM is effective in HR-positive disease, but not in HR-negative disease.
Oncogenicity of the Developmental Transcription Factor Sox9
Authors: Ander Matheu, Manuel Collado, Clare Wise, Lorea Manterola, Lina Cekaite, Angela J. Tye, Marta Canamero, Luis Bujanda, Andreas Schedl, Kathryn S.E. Cheah, Rolf I. Skotheim, Ragnhild A. Lothe, Adolfo López de Munain, James Briscoe, Manuel Serrano, Robin Lovell-Badge
Journal: Cancer Research (2012)

Abstract SOX9 [sex-determining region Y (SRY)-box 9 protein], a high mobility group box transcription factor, plays critical roles during embryogenesis and its activity is required for development, differentiation, and lineage commitment in various tissues including the intestinal epithelium. Here, we present functional and clinical data of a broadly important role for SOX9 in tumorigenesis. SOX9 was overexpressed in a wide range of human cancers, where its expression correlated with malignant character and progression. Gain of SOX9 copy number is detected in some primary colorectal cancers. SOX9 exhibited several pro-oncogenic properties, including the ability to promote proliferation, inhibit senescence, and collaborate with other oncogenes in neoplastic transformation. In primary mouse embryo fibroblasts and colorectal cancer cells, SOX9 expression facilitated tumor growth and progression whereas its inactivation reduced tumorigenicity. Mechanistically, we have found that Sox9 directly binds and activates the promoter of the polycomb Bmi1, whose upregulation represses the tumor suppressor Ink4a/Arf locus. In agreement with this, human colorectal cancers showed a positive correlation between expression levels of SOX9 and BMI1 and a negative correlation between SOX9 and ARF in clinical samples. Taken together, our findings provide direct mechanistic evidence of the involvement of SOX9 in neoplastic pathobiology, particularly, in colorectal cancer. Cancer Res; 72(5); 1301–15. ©2012 AACR.
Doctors' leaders call for "bold" step to ban smoking in private cars
Authors: A. O'Dowd
Journal: BMJ (2011)

The government should take a “bold” step to legislate for a ban on smoking in private cars in the United Kingdom, claim doctors’ leaders.

The BMA has called on the four UK administrations to introduce an extension to current smoke free legislation to include a ban on smoking in private cars, claiming there is compelling scientific evidence to support the move.

The Department of Health, however, has rejected the call, saying there are better ways to encourage behaviour change and promising to launch a publicity campaign next year on the dangers of second hand smoke.

MPs are due to debate the issue on 25 November when the House of Commons will have a second reading of Labour …
Decision Support for Patients With Early-Stage Breast Cancer: Effects of an Interactive Breast Cancer CDROM on Treatment Decision, Satisfaction, and Quality of Life
Authors: Sjaak Molenaar, Mirjam AG Sprangers, Emiel J. Th. Rutgers, Ernest JT Luiten, Jan Mulder, Patrick MM Bossuyt, Jannes JE van Everdingen, Paul Oosterveld, Hanneke CJM de Haes
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To investigate the effects of the Interactive Breast Cancer CDROM as a decision aid for breast cancer patients with a choice between breast conserving therapy (BCT) and mastectomy (MT). PATIENTS AND METHODS: Consecutive patients with stage I and II breast cancer were enrolled. A quasi-experimental, longitudinal, and pretest/posttest design was used. Follow-up was scheduled 3 and 9 months after discharge from the hospital. Control patients (n = 88) received standard care (oral information and brochures). The CDROM was provided to patients in the experimental condition (n = 92) as a supplement to standard procedures. Outcome variables were treatment decision, satisfaction, and quality of life (QoL). RESULTS: No effect on treatment decision was found. CDROM patients expressed more general satisfaction with information at 3 and 9 months (95% confidence interval for the difference (d) between the means (d: 4.1 to 12.5 and 5.7 to 14.2 respectively). CDROM patients were also more satisfied with their treatment decision at 3 and at 9 months (d: 0.1 to 0.4; 0.2 to 0.5). Moreover, at 9 months, CDROM patients were more satisfied with breast cancer–specific information (d: 0.9 to 16.5), the decision-making process (d: 0.1 to 0.4), and communication (d: 0.2 to 11.0). At 3 and 9 months, a positive effect was found on general health (d: 0.2 to 14.5 and 0.3 to 15.0). Moreover, at 9 months, CDROM patients reported better physical functioning (d: 5.1 to 19.8), less pain (d: -17.9 to -4.5), and fewer arm symptoms (d: -14.1 to -0.5). CONCLUSION: The Interactive Breast Cancer CDROM improved decision making in patients with early-stage breast cancer with a choice between BCT and MT, as evaluated in terms of patients’ satisfaction and QoL.
Where to place the Doppler sample volume in the human main pulmonary artery: evaluated from magnetic resonance phase velocity maps
Authors: Erik Sloth, Kim C. Houlind, Erik M. Pedersen, J.Michael Hasenkam
Journal: Cardiovascular Research (1997)

Objective: To give recommendations for the placement of Doppler sample volumes for blood flow assessment in the human main pulmonary artery. Methods: In 10 healthy volunteers MR-phase velocity measurements were obtained and computing of the mean temporal blood velocity data was performed to guide single point Doppler velocity recordings. Results: The mean temporal blood velocity profiles were consistently skewed with the lowest blood velocities towards the inferior/right vessel wall. Blood velocity indices (ratio of point to mean velocities, where a point equals a square of 4 pixels) varied considerably with the lowest indices located towards the inferior/right vessel wall. A centrally located fictive sample volume revealed an average blood velocity index value (average of all 10 subjects) of 1.08 (range 0.99–1.25; s.d. 0.08) where the central point was defined at maximum systole, and a value of 1.13 (range 0.97–1.34; s.d. 0.11) when the central point was defined in end-diastole. The mean of multiple sample volumes along the inferior/right to superior/left diameter revealed a blood velocity index of 1.01 (range 0.87–1.21; s.d. 0.09) in systole and 1.03 (range 0.87–1.19; s.d. 0.09) in diastole. Conclusions: For practical clinical purposes, single point estimation of the mean blood velocity in the pulmonary artery should be performed centrally. The use of multiple sample volumes placed along the inferior/right to superior/left diameter improves the mean velocity estimate in healthy volunteers. Further studies should be conducted to reinforce the basis for Doppler velocity recording in the diseased human pulmonary artery as well as to investigate other important determinants of Doppler-derived CO, namely angle of insonation and assessment of the cross-sectional area.
Gastrin Releasing Peptide-Preferring Bombesin Receptors Mediate Growth of Human Renal Cell Carcinoma
Authors: ANDREAS PANSKY, ANDREAS DE WEERTH, ELIZAVETA FASLER-KAN, JEAN-LOUIS BOULAY, MARTINA SCHULZ, SYLVIA KETTERER, CRISTIN SELCK, CHRISTOPH BEGLINGER, TAMMO VON SCHRENCK, PIUS HILDEBRAND
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Bombesin-like peptides typically act as neurotransmitters along the brain-gut axis and as growth factors in various human tissues. The present study demonstrates the expression of gastrin releasing peptide (GRP)-preferring bombesin receptors in human renal cell carcinoma but not in normal kidney tissue. The expression of GRP receptors was characterized at the mRNA level by reverse transcription-PCR, as well as at the protein level by binding of 125 I-[Tyr 4 ] bombesin to membranes prepared from tumor tissue ( K d 0.3 nM) and healthy kidney tissue from the same four patients. GRP receptors were also demonstrated in four human kidney carcinoma cell lines (A-498, CAKI-1, CAKI-2, and ACHN). The effects of bombesin/GRP agonists and/or antagonists on growth were investigated in vitro on CAKI-2 cells, which expressed large amounts of GRP receptors. Cell numbers stimulated by 10% fetal calf serum were significantly stimulated by interleukin-1β (control) and GRP-7 (10 -7 M), both in the range of 136 to 148%; addition of the GRP receptor antagonist acetyl-GRP(20-27) (10 -6 M) completely reversed this effect. Bombesin alone (10 -6 M) significantly stimulated CAKI-2 cells (129%) cultured with 0.5% fetal calf serum, whereas another antagonist, D-Phe6,Leu13,(CH2NH)Leu14 bombesin(6-14) (1 μM), alone did not inhibit growth, thus excluding an autocrine mechanism. These results indicate for the first time that malignant transformation of human kidney tissue into renal cell carcinoma is accompanied by novel expression of GRP receptors. Bombesin-like peptides might act as mitogens in these carcinomas, and they might be useful as diagnostic or therapeutic tools such as tumor imaging or internal radiotherapy.
Variations of Ambulatory Blood Pressure With Position in Patients With Type 1 Diabetes
Authors: Pierre Y. Benhamou, Sandrine Mouret, Jean L. Quesada, Robert Boizel, Jean P. Baguet, Serge Halimi, Jean M. Mallion
Journal: Diabetes Care (2001)

OBJECTIVE—To study the influence of position changes on 24-h ambulatory blood pressure (ABP) in normotensive or mildly hypertensive normoalbuminuric patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—A cross-sectional evaluation of patients was staged according to the duration of diabetes (DD) and the presence of microangiopathy. We recruited 37 patients (30 men and 7 women), aged 38 ± 12 years, who were normotensive or mildly hypertensive (diastolic blood pressure [DBP] &amp;lt;105 mmHg) and free of antihypertensive treatment and microalbuminuria. They were included according to DD (group 1, &amp;lt;5 years; group 2, ≥10 years). An additional group of seven diabetic patients with microalbuminuria and mild untreated hypertension was also investigated. We recorded 24-h ambulatory blood pressure every 15 min with a position sensor, which allowed for the discrimination between standing or supine/sitting position in the patient. RESULTS—Mean daytime (10:00 a.m. to 8:00 p.m.) ABP in supine/sitting position did not significantly differ between groups 1 and 2. However, standing ambulatory systolic blood pressure (ASBP) and ambulatory DBP (ADBP) were significantly higher than supine/sitting ASBP and ADBP in group 1 (ΔSBP 4 ± 5, ΔDPB 4 ± 6 mmHg, P &amp;lt; 0.01) but not in group 2 (ΔSBP 2 ± 8, ΔDBP 2 ± 4 mmHg, P = NS). Patients free of microangiopathy presented with significantly higher ABP in standing position than in sitting/lying position, whereas patients with retinopathy and/or nephropathy exhibited no significant increase of ABP during standing. CONCLUSION—The monitoring of position during ambulatory measurement of blood pressure in type 1 diabetic patients shows different patterns in relation to disease duration and the presence of microangiopathy.
Vaccination With Irradiated Autologous Tumor Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor Augments Antitumor Immunity in Some Patients With Metastatic Non–Small-Cell Lung Carcinoma
Authors: Ravi Salgia, Thomas Lynch, Arthur Skarin, Joan Lucca, Cathleen Lynch, Ken Jung, F. Stephen Hodi, Michael Jaklitsch, Steve Mentzer, Scott Swanson, Jean Lukanich, Raphael Bueno, John Wain, Douglas Mathisen, Cameron Wright, Panos Fidias, Dean Donahue, Shirley Clift, Steve Hardy, Donna Neuberg, Richard Mulligan, Iain Webb, David Sugarbaker, Martin Mihm, Glenn Dranoff
Journal: Journal of Clinical Oncology (2003)

We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non-small-cell lung cancer (NSCLC), we conducted a phase I clinical trial.Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 x 10(6), 4 x 10(6), or 1 x 10(7) cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals.Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/10(6) cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed.Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC.
Evolution of Analytical Performance in Portable Glucose Meters in the Last Decade
Authors: Philip Böhme, Michele Floriot, Marie-Aude Sirveaux, Danielle Durain, Olivier Ziegler, Pierre Drouin, Bruno Guerci
Journal: Diabetes Care (2003)

To assess and compare the technical accuracy of portable glucose meters during the last decade.One-thousand preprandial (pre) and postprandial (post) capillary whole-blood glucose values measured with meters owned mainly by diabetic patients were compared with a single laboratory method yearly from 1989 to 1999. A total of 21,950 capillary measurements and their corresponding laboratory reference values were analyzed at our clinic.The lowest mean absolute difference was found in 1989 (pre: 2 +/- 22 mg/dl, post: 9 +/- 31 mg/dl) (mean +/- SD). The highest mean absolute difference was observed in 1993 (pre: 31 +/- 33 mg/dl) and 1996 (post: 50 +/- 35 mg/dl). The highest mean relative deviation was observed in 1990 (pre: 16.4%) and 1996 (post: 20.6%). The highest percentage of readings that were within a 5% deviation limit were observed in 1998 (pre: 44.5%) and in 1997 (post: 36.7%). Based on blood glucose levels within +/-5 and +/-10% of laboratory values, the technical accuracy of meters was similar for 1989 and 1999 (P = 0.27 and 0.52, respectively). The percentage of pre values in zone A of Clarke's error grid analysis was >90% in 1989, 1997, 1998, and 1999.The analytical performance of glucose meters decreased between 1990 and 1996 but was restored between 1997 and 1999. Nevertheless, our data suggest that the technical accuracy of glucose meters has not significantly improved during the last decade. Complementary studies taking into account the preanalytical improvements of the recent meters, as well as their calibration method, appear necessary.
Swainsonine reduces 5-fluorouracil tolerance in the multistage resistance of colorectal cancer cell lines
Authors: Jun Hamaguchi, Hiroaki Nakagawa, Masato Takahashi, Takeaki Kudo, Naoya Kamiyama, Bailong Sun, Takahiro Oshima, Yuji Sato, Kisaburo Deguchi, Satoru Todo, Shin-Ichiro Nishimura
Journal: Molecular Cancer (2007)

Abstract Background Drug resistance is a major problem in cancer chemotherapy. Acquisition of chemo-resistance not only reduces the effectiveness of drugs, but also promotes side effects and markedly reduces the patient's quality of life. However, a number of resistance mechanisms have been reported and are thought to be the reason for the difficulties in solving drug-resistance problems. Result To investigate the mechanisms of drug resistance, a set of cell lines with different levels of sensitivity and possessing different mechanisms of resistance to 5-fluorouracil (5-FU) was established from a colorectal cancer cell line. The expression of thymidylate synthase, orotic acid phosphoribosyltransferase and dihydropyrimidine dehydrogenase, which are well known to be related to drug resistance, differed among these cell lines, indicating that these cell lines acquired different resistance mechanisms. However, swainsonine, an inhibitor of N-glycan biosynthesis, reduced 5-FU-tolerance in all resistant cells, whereas the sensitivity of the parental cells was unchanged. Further analysis of the N-glycan profiles of all cell lines showed partial inhibition of biosynthesis and no cytotoxicity at the swainsonine dosage tested. Conclusion These observations suggest that N-linked oligosaccharides affect 5-FU resistance more widely than do drug-resistance related enzymes in colorectal cancer cells, and that the N-glycan could be a universal target for chemotherapy. Further, swainsonine may enhance the performance of chemotherapy by reducing tolerance.