tbuckley/cabot-search huggingface dataset:
Circulating Tumor Cells and Response to Chemotherapy in Metastatic Breast Cancer: SWOG S0500
Authors: Jeffrey B. Smerage, William E. Barlow, Gabriel N. Hortobagyi, Eric P. Winer, Brian Leyland-Jones, Gordan Srkalovic, Sheela Tejwani, Anne F. Schott, Mark A. O'Rourke, Danika L. Lew, Gerald V. Doyle, Julie R. Gralow, Robert B. Livingston, Daniel F. Hayes
Journal: Journal of Clinical Oncology (2014)

Purpose Increased circulating tumor cells (CTCs; five or more CTCs per 7.5 mL of whole blood) are associated with poor prognosis in metastatic breast cancer (MBC). A randomized trial of patients with persistent increase in CTCs tested whether changing chemotherapy after one cycle of first-line chemotherapy would improve the primary outcome of overall survival (OS). Patients and Methods Patients with MBC who did not have increased CTCs at baseline remained on initial therapy until progression (arm A). Patients with initially increased CTCs that decreased after 21 days of therapy remained on initial therapy (arm B). Patients with persistently increased CTCs after 21 days of therapy were randomly assigned to continue initial therapy (arm C1) or change to an alternative chemotherapy (arm C2). Results Of 595 eligible and evaluable patients, 276 (46%) did not have increased CTCs (arm A). Of those with initially increased CTCs, 31 (10%) were not retested, 165 were assigned to arm B, and 123 were randomly assigned to arm C1 or C2. No difference in median OS was observed between arm C1 and C2 (10.7 and 12.5 months, respectively; P = .98). CTCs were strongly prognostic. Median OS for arms A, B, and C (C1 and C2 combined) were 35 months, 23 months, and 13 months, respectively (P &lt; .001). Conclusion This study confirms the prognostic significance of CTCs in patients with MBC receiving first-line chemotherapy. For patients with persistently increased CTCs after 21 days of first-line chemotherapy, early switching to an alternate cytotoxic therapy was not effective in prolonging OS. For this population, there is a need for more effective treatment than standard chemotherapy.
The small molecule, genistein, increases hepcidin expression in human hepatocytes
Authors: Aileen W. Zhen, Nancy H. Nguyen, Yann Gibert, Shmulik Motola, Peter Buckett, Marianne Wessling-Resnick, Ernest Fraenkel, Paula G. Fraenkel
Journal: Hepatology (2013)

Hepcidin, a peptide hormone that decreases intestinal iron absorption and macrophage iron release, is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. Endogenous stimulants of Hepcidin transcription include bone morphogenic protein 6 (BMP6) and interleukin-6 (IL-6) by effects on mothers against decapentaplegic homolog (Smad)4 or signal transducer and activator of transcription (Stat)3, respectively. We conducted a small-scale chemical screen in zebrafish embryos to identify small molecules that modulate hepcidin expression. We found that treatment with the isoflavone, genistein, from 28-52 hours postfertilization in zebrafish embryos enhanced Hepcidin transcript levels, as assessed by whole-mount in situ hybridization and quantitative real-time reverse-transcriptase polymerase chain reaction. Genistein's stimulatory effect was conserved in human hepatocytes: Genistein treatment of HepG2 cells increased both Hepcidin transcript levels and promoter activity. We found that genistein's effect on Hepcidin expression did not depend on estrogen receptor signaling or increased cellular iron uptake, but was impaired by mutation of either BMP response elements or the Stat3-binding site in the Hepcidin promoter. RNA sequencing of transcripts from genistein-treated hepatocytes indicated that genistein up-regulated 68% of the transcripts that were up-regulated by BMP6; however, genistein raised levels of several transcripts involved in Stat3 signaling that were not up-regulated by BMP6. Chromatin immunoprecipitation and ELISA experiments revealed that genistein enhanced Stat3 binding to the Hepcidin promoter and increased phosphorylation of Stat3 in HepG2 cells. Conclusion : Genistein is the first small-molecule experimental drug that stimulates Hepcidin expression in vivo and in vitro . These experiments demonstrate the feasibility of identifying and characterizing small molecules that increase Hepcidin expression. Genistein and other candidate molecules may subsequently be developed into new therapies for iron overload syndromes. (Hepatology 2013;58:1315–1325)
CD4<b>+</b>CD25<b>+</b> T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function
Authors: Ian P. Lewkowich, Nancy S. Herman, Kathleen W. Schleifer, Matthew P. Dance, Brian L. Chen, Krista M. Dienger, Alyssa A. Sproles, Jaimin S. Shah, Jörg Köhl, Yasmine Belkaid, Marsha Wills-Karp
Journal: The Journal of Experimental Medicine (2005)

The role of natural CD4+CD25+ regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness (AHR). In C3H mice, anti-CD25-mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis (AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 (Th2) cytokine production. In similarly T reg cell-depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells (DCs) in T reg cell-depleted C3H mice. T reg cell-depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell-depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4+CD25+ T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility.
Results of a Randomized Trial of Chlorambucil Versus Fludarabine for Patients With Untreated Waldenström Macroglobulinemia, Marginal Zone Lymphoma, or Lymphoplasmacytic Lymphoma
Authors: Véronique Leblond, Steve Johnson, Sylvie Chevret, Adrian Copplestone, Simon Rule, Olivier Tournilhac, John Francis Seymour, Russell D. Patmore, David Wright, Pierre Morel, Marie-Sarah Dilhuydy, Sara Willoughby, Caroline Dartigeas, Marion Malphettes, Bruno Royer, Maeve Ewings, Guy Pratt, Julie Lejeune, Florence Nguyen-Khac, Sylvain Choquet, Roger G. Owen
Journal: Journal of Clinical Oncology (2012)

Purpose Treatment options for patients with Waldenström macroglobulinemia (WM) and closely related disorders include alkylating agents, purine analogs, and monoclonal antibodies. No large randomized studies have yet been reported comparing any of these approaches. Patients and Methods The randomized WM1 study (Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia) was undertaken in 101 centers in five countries enrolling 414 eligible patients (339 with WM, 37 with non–mucosa-associated lymphoid tissue marginal zone lymphoma, and 38 with lymphoplasmacytic lymphoma) who were randomly assigned to receive chlorambucil or fludarabine. The primary end point was the overall response rate (ORR). Results On the basis of intent-to-treat analysis, the ORR was 47.8% (95% CI, 40.9% to 54.8%) in the fludarabine arm versus 38.6% (95% CI, 32.0% to 45.7%) in the chlorambucil arm (P = .07). With a median follow-up of 36 months (interquartile range, 18 to 58 months), median progression-free survival (PFS), and duration of response (DR) were significantly improved in the fludarabine arm compared with the chlorambucil arm: PFS, 36.3 versus 27.1 months (P = .012) and DR, 38.3 versus 19.9 months (P &lt; .001). In patients with WM, median overall survival (OS) was not reached in the fludarabine arm versus 69.8 months in the chlorambucil arm (95% CI, 61.6 to 79.8 months; P = .014). Grade 3 to 4 neutropenia was significantly higher among patients treated with fludarabine (36%) compared with patients treated with chlorambucil (17.8%; P &lt; .001). Second malignancies were significantly more frequent in the chlorambucil arm with 6-year cumulative incidence rate of 20.6% versus 3.7% in the fludarabine arm (P = .001). Conclusion In the complete intent-to-treat study population, fludarabine significantly improved PFS compared with chlorambucil, and in patients with WM, it improved OS.
SPECIFICITY OF CELLULAR IMMUNE RESPONSES
Authors: William E. Paul, Gregory W. Siskind, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1968)

In vitro antigen stimulation of DNA synthesis in lymph node cultures from immunized guinea pigs can be obtained with very low (10(-4) microg/ml) antigen concentrations in the culture fluid. Immunization with low doses of DNP-GPA leads to a cell population capable of being stimulated, on the average, by low concentration of antigen whereas immunization with large antigen doses results in a sensitive cell population requiring, on the average, high antigen concentrations for stimulation. These findings correlate well with the affinity for hapten of the serum antibodies produced by these guinea pigs. Both delayed reactions in vivo and DNA synthesis in vitro can be stimulated by hapten conjugated to proteins different from that used in primary immunization. However the immunizing conjugate is much more effective in terms of antigen concentration required for a given response. These results can be understood in terms of a thermodynamically driven interaction of antigen (or "processed" antigen) with cell-associated antibody.
Paying for Care Episodes and Care Coordination
Authors: Karen Davis
Journal: New England Journal of Medicine (2007)

The fee-for-service system of provider payment is increasingly viewed as an obstacle to achieving effective, coordinated, and efficient care.1 It rewards the overuse of services, duplication of services, use of costly specialized services, and involvement of multiple physicians in the treatment of individual patients. It does not reward the prevention of hospitalization or rehospitalization, effective control of chronic conditions, or care coordination.Pay for performance is one strategy for moving from payment based solely on the quantity of services rendered to payment based on the quality or efficiency of care.2 Such payment systems are now widely used in private health . . .
Preoperative cardiac catheterization. Its need in most patients with valvular heart disease
Authors: R. A. O'Rourke
Journal: JAMA (1982)

DECISIONS concerning the optimal time for cardiac surgery in patients with valvular heart disease are often extremely difficult. Factors to be considered when recommending valve replacement include the patient's symptoms and physical findings; the severity of valvular obstruction or regurgitation, or both; the natural history of the disease process; the presence of normal or abnormal ventricular performance; the presence or absence of coexistent coronary artery disease; and the morbidity and mortality associated with valve replacement.<sup>1-5</sup> During the past two decades, cardiac catheterization with cineangiography, and often with selective coronary arteriography, has been the "gold standard" for determining the extent of valvular obstruction or regurgitation, or both, the number of cardiac valves affected, the effects of valvular disease on resting and exercise cardiac hemodynamics, the presence of normal or reduced left ventricular (LV) performance, and the existence or absence of important coincident coronary artery disease. Noninvasive techniques, particularly echocardiography and
Hepatitis B vaccination of newborn infants: Clinical study of new vaccine formulation and dose regimen
Authors: Keun Soo Lee, Hahng Lee, Soo Jee Moon, Kyu Jong Choi, Ki Hong Kim, Chun Won Kim, Wha Soon Chung, Tae Yael Choi
Journal: Hepatology (1987)

To investigate the efficacy in anti-HBsAg response with half the recommended adult dose in a standard vaccination schedule or with a full dose in reduced number of vaccination schedule, 201 healthy newborn infants were randomized to receive either 2.5 μg Hevac B vaccine at birth [1, 2 and 14 months in Group I (101)] or 5 μg at birth [2 and 14 months in Group II (100)]. Anti-HBsAg responses in the two groups were compared. Passively acquired anti-HBsAg positivity rates at birth were 51.5 and 45.0% in Groups I and II, respectively. Cumulative anti-HBsAg seroconversion rates in Group I were 12.2, 76.6, 82.6 and 86.4% at 2, 4, 14 and 16 months, while the rates in Group II were 2.5, 62.5, 73.7 and 91.0%, showing no significant difference (p &gt; 0.05). Significant difference in seroconversion rates at the 2-month follow-up stage between passively acquired anti-HBsAg-negative and -positive groups was observed (11.9 vs. 2.6%). Significant rise in anti-HBsAg titer at 16 months following the booster at 14 months was noted: 36.4 mIU per ml before, 546.4 mIU per ml after in Group I and 25.3 mIU per ml before, 782.6 mIU per ml after in Group II. The booster, 12 months after the primary vaccination series, is therefore considered imperative for maximum effectiveness of hepatitis B active immunization. Although the present programs of unselective vaccination with modified dose schedules were ineffective for lowering the number of persistent HBsAg carriers for the high-risk newborn infants exposed to HBsAg- and HBeAg-positive mothers, and the high-risk group infants were not excluded in this study, the over-all effectiveness of these programs is considered comparable to that of the currently recommended standard dose schedule for immunization of low-risk newborn infants.
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM
Authors: Werner Henle, Gertrude Henle
Journal: The Journal of Experimental Medicine (1949)

In agreement with earlier observations the infectivity titer in the allantoic fluids of chick embryos injected with influenza A virus remains constant for 5 to 6 hours before an increase in this activity can be noted. In contrast, the titers of hemagglutinin and complement-fixing antigen (virus antigen) have already begun to rise after 3 hours. The origin of the hemagglutinating and complement-fixing but non-infectious material is still obscure. In the allantoic membrane development of both the soluble and virus antigens can be demonstrated after the 2nd hour of incubation and 1 hour prior to an increase in hemagglutinins and 2 hours prior to a rise in infectivity. Thus there remain the first 2 hours during which no record of virus activity in the tissues can be obtained. Similar relationships are noted on dilution of the seed both in the allantoic fluids and membranes as long as the various properties reach measurable levels during the experimental period of one infectious cycle. Injection of high titered immune serum following infection with about 109 ID50 reduces the amount of demonstrable seed virus in the allantoic fluid and membrane without significantly affecting propagation of the agent in the tissues as measured by infectivity titrations. The production of hemagglutinins appears markedly reduced under these conditions whereas formation of complement-fixing antigen is only slightly delayed and decreased. No definite explanations for the various discrepancies between the infectivity and hemagglutination can be given at present.
Involvement in treatment decisions: what do adults with asthma want and what do they get? Results of a cross sectional survey
Authors: Caress A, Beaver K, Luker Ka, Campbell Mg, A A Woodcock
Journal: Thorax (2005)

<b>Background:</b> Current healthcare policy advocates patient participation in treatment decision making. However, in asthma there is little evidence regarding patients' views on such involvement. This study explored the preferred and perceived level of involvement in treatment decisions, rationales for role preference, perceived facilitators of/barriers to involvement, and the interrelationship of role preference and demographic variables in a sample of patients with asthma. <b>Methods:</b> A cross sectional survey was performed of 230 adults with clinician diagnosed asthma from 10 primary care sites and one specialist respiratory centre in north-west England. Preferred role in treatment decisions was assessed using the Control Preferences Scale. <b>Results:</b> Fifty five (23.9%) preferred an active role, 82 (35.7%) a collaborative role, and 93 (40.4%) a passive role; 19 (8.2%) perceived their role as active compared with 45 (19.6%) collaborative and 166 (72.2%) passive. Only 33.5% (n = 77) of respondents attained their most preferred role; 55.2% (n = 127) were less involved than they preferred. Patient related, professional related, and organisational factors, especially quality and duration of consultations, facilitated or hampered involvement. Role preferences were not strongly associated with demographic variables or asthma severity. <b>Conclusions:</b> This study in patients with asthma highlights the fact that there is a need for professional and patient education regarding partnership working, skilful communication, and innovative approaches to service delivery.
Early Versus Delayed Initiation of Concurrent Palliative Oncology Care: Patient Outcomes in the ENABLE III Randomized Controlled Trial
Authors: Marie A. Bakitas, Tor D. Tosteson, Zhigang Li, Kathleen D. Lyons, Jay G. Hull, Zhongze Li, J. Nicholas Dionne-Odom, Jennifer Frost, Konstantin H. Dragnev, Mark T. Hegel, Andres Azuero, Tim A. Ahles
Journal: Journal of Clinical Oncology (2015)

Purpose Randomized controlled trials have supported integrated oncology and palliative care (PC); however, optimal timing has not been evaluated. We investigated the effect of early versus delayed PC on quality of life (QOL), symptom impact, mood, 1-year survival, and resource use. Patients and Methods Between October 2010 and March 2013, 207 patients with advanced cancer at a National Cancer Institute cancer center, a Veterans Affairs Medical Center, and community outreach clinics were randomly assigned to receive an in-person PC consultation, structured PC telehealth nurse coaching sessions (once per week for six sessions), and monthly follow-up either early after enrollment or 3 months later. Outcomes were QOL, symptom impact, mood, 1-year survival, and resource use (hospital/intensive care unit days, emergency room visits, chemotherapy in last 14 days, and death location). Results Overall patient-reported outcomes were not statistically significant after enrollment (QOL, P = .34; symptom impact, P = .09; mood, P = .33) or before death (QOL, P = .73; symptom impact, P = .30; mood, P = .82). Kaplan-Meier 1-year survival rates were 63% in the early group and 48% in the delayed group (difference, 15%; P = .038). Relative rates of early to delayed decedents' resource use were similar for hospital days (0.73; 95% CI, 0.41 to 1.27; P = .26), intensive care unit days (0.68; 95% CI, 0.23 to 2.02; P = .49), emergency room visits (0.73; 95% CI, 0.45 to 1.19; P = .21), chemotherapy in last 14 days (1.57; 95% CI, 0.37 to 6.7; P = .27), and home death (27 [54%] v 28 [47%]; P = .60). Conclusion Early-entry participants' patient-reported outcomes and resource use were not statistically different; however, their survival 1-year after enrollment was improved compared with those who began 3 months later. Understanding the complex mechanisms whereby PC may improve survival remains an important research priority.
Autologous Umbilical Cord Blood Transfusion in Young Children With Type 1 Diabetes Fails to Preserve C-Peptide
Authors: Michael J. Haller, Clive H. Wasserfall, Maigan A. Hulme, Miriam Cintron, Todd M. Brusko, Kieran M. McGrail, Theresa M. Sumrall, John R. Wingard, Douglas W. Theriaque, Jonathan J. Shuster, Mark A. Atkinson, Desmond A. Schatz
Journal: Diabetes Care (2011)

OBJECTIVE We conducted an open-label, phase I study using autologous umbilical cord blood (UCB) infusion to ameliorate type 1 diabetes (T1D). Having previously reported on the first 15 patients reaching 1 year of follow-up, herein we report on the complete cohort after 2 years of follow-up. RESEARCH DESIGN AND METHODS A total of 24 T1D patients (median age 5.1 years) received a single intravenous infusion of autologous UCB cells and underwent metabolic and immunologic assessments. RESULTS No infusion-related adverse events were observed. β-Cell function declined after UCB infusion. Area under the curve C-peptide was 24.3% of baseline 1 year postinfusion (P &amp;lt; 0.001) and 2% of baseline 2 years after infusion (P &amp;lt; 0.001). Flow cytometry revealed increased regulatory T cells (Tregs) (P = 0.04) and naive Tregs (P = 0.001) 6 and 9 months after infusion, respectively. CONCLUSIONS Autologous UCB infusion in children with T1D is safe and induces changes in Treg frequency but fails to preserve C-peptide.
Video analysis of causes and mechanism of the ACL injuries in the Iranian professional soccer player
Authors: Hamed Tarmah, Nader Rahnama, Khalil Khayyambashi
Journal: British Journal of Sports Medicine (2010)

Soccer is one of the most popular and high-risk sports around the world. The highest number of injuries in this sport occurs in the knee joint and anterior cruciate ligament (ACL). The aim of this study was to examine the causes and mechanism of ACL injuries among the Iranian professional soccer players. Fifteen professional soccer players (age: 25±3.48 years, height: 179.13±4.61 cm, weight: 72.6±4.43 kg) who suffered from ACL injury were studied. Information was collected via watching the video of the matches and interviewing with the team physicians and studying the medical files and reports. The result of this study showed that the number of non-contact injuries (73.3%) was significantly more than that of contact (26.7%) injuries (χ 2 =3.26, p&lt;0.05) and most of the injuries occurred in the dominant leg. Regarding the severity of the injuries, most of them were severe and needed surgery (χ 2 =11.26, p&lt;0.05). Although the number of injuries during the match was greater than practice, the differences were not significant. The main causes of non-contact injuries were a sudden change in direction (χ 2 =5.09, p&lt;0.05). Most of the injuries occurred in the away matches (χ 2 =3.6, p&lt;0.05) and in the end of the competition season. No significant differences were found between playing positions. It is noteworthy that most of the injuries occurred during the first half of the match and during 31–45 min (χ 2 =10.8, p&lt;0.05). It can be concluded that most of the ACL injuries are non-contact and sudden change in direction is the main cause of injury. This information can be used in planning preventive programmes.