tbuckley/cabot-search huggingface dataset:
The Human Vaccines Project: A roadmap for cancer vaccine development
Authors: Pedro Romero, Jacques Banchereau, Nina Bhardwaj, Mark Cockett, Mary L. Disis, Glenn Dranoff, Eli Gilboa, Scott A. Hammond, Robert Hershberg, Alan J. Korman, Pia Kvistborg, Cornelis Melief, Ira Mellman, A. Karolina Palucka, Irina Redchenko, Harlan Robins, Federica Sallusto, Theodore Schenkelberg, Stephen Schoenberger, Jeffrey Sosman, Özlem Türeci, Benoît Van den Eynde, Wayne Koff, George Coukos
Journal: Science Translational Medicine (2016)

A concerted international effort is necessary to achieve clinically effective cancer vaccines.
Temporal trends in small cell lung cancer: Analysis of the national Surveillance, Epidemiology, and End-Results (SEER) database
Authors: S. Navada, P. Lai, A. G. Schwartz, G. P. Kalemkerian
Journal: Journal of Clinical Oncology (2006)

7082 Background: Research interest in small cell lung cancer (SCLC) has waned over the past 10 years due to the lack of significant therapeutic advances and a presumed decline in the incidence of SCLC. Methods: We analyzed data on all patients with primary bronchogenic carcinoma registered in the national SEER database from 1973–2002. To identify temporal trends, the study period was divided into three decades: 1973–1982 (D1), 1983–1992 (D2), and 1993–2002 (D3). Results: Of 318,584 eligible patients, 59,704 (18.7%) had SCLC. The proportional incidence of SCLC relative to non-SCLC was higher in Caucasians than African-Americans (19.6% vs 13.9%), women vs men (21% vs 17.4%), and patients ≥ 50 yrs old vs &lt; 50 yrs old (18.9% vs 16%). By decade, the proportional incidence of SCLC was: D1, 18.4%; D2, 19.8%; D3, 17.9%. The overall incidence rates for both SCLC and non-SCLC initially rose and then declined during the study period. The incidence rates for SCLC were similar in both Caucasians and African-Americans throughout the study period, while those for non-SCLC were significantly higher in African-Americans. The gap between incidence rates in men and women has narrowed to a similar degree for both SCLC (M/F: D1, 2.6/1 to D3 1.4/1) and NSCLC (M/F: D1, 3.3/1 to D3, 1.7/1). Only 0.8% of SCLC patients underwent surgical resection from 1988–2002. The use of radiotherapy decreased during the study period (D1, 53% to D3, 43%) with greater use in younger patients and African-Americans. Stage-specific 2- and 5-year survival rates for SCLC improved over time (regional 2-yr/5-yr: D1, 15%/6.8% to D3, 22%/11%; distant 2-yr/5-yr: D1, 3.4%/1.3% to D3, 5.6%/1.9%). In multivariate analysis, significant favorable prognostic factors included: younger age, Caucasian race, female gender, limited stage, and later year of diagnosis. Conclusions: The proportional incidence of SCLC has declined only slightly over the past three decades. While overall survival has modestly improved, SCLC remains a major public health problem. No significant financial relationships to disclose.
Activation of Serum Lactic Dehydrogenase
Authors: Louis Cohen, Lawrence Larson
Journal: New England Journal of Medicine (1966)

THREE lactic acid dehydrogenase (LDH) isozyme patterns are known to be associated with increased serum LDH activities1 (Fig. 1). One common pattern, called the alpha LDH abnormality, is associated with erythrocyte hemolysis and with injuries of the renal cortex and myocardium. A second common pattern, called the beta-gamma LDH abnormality, is associated with injuries of the liver, skeletal muscle and skin. A much less common pattern, called the isomorphic LDH abnormality, is associated with some types of proliferative and disseminated neoplastic diseases. The alpha and beta-gamma LDH abnormalities precisely reflect the LDH isozyme patterns found in the . . .
P21 The applicability of current cardiovascular risk scores and cardiovascular surrogates in chronic obstructive pulmonary disease: A case-control study
Authors: IS Stone, MJ Khanji, W-Y James, A Balawon, R Boubertakh, L John, NC Barnes, SE Petersen
Journal: Thorax (2015)

<h3>Background</h3> COPD is a complex multi-morbid disorder with significant cardiac mortality. Despite this, current cardiovascular scoring systems do not include COPD in their risk prediction models. The aims of this study were to assess whether differences in cardiovascular surrogate markers exist in COPD and to further our understanding of the relationship of COPD to cardiovascular structure and function. <h3>Methods</h3> This post-hoc cross-sectional analysis utilised baseline data from two randomised controlled trials (n = 36 and 54). 26 COPD patients were matched for global cardiovascular risk with 26 controls with normal lung function using QRISK2, a validated scoring system for predicting the 10-year risk of cardiovascular disease in a United Kingdom population. Patients underwent cardiac magnetic resonance imaging, arterial stiffness and lung function measurements. <h3>Results</h3> Pulse wave velocity (PWV) (mean difference +1.0 m/s, 95% CI 0.02–1.92; p = 0.045) and total arterial compliance (TAC) (mean difference -0.27 mL/m<sup>2</sup>/mmHg, 95% CI -0.39, -0.15; p &lt; 0.001) were adversely affected in COPD compared to the control group matched for cardiovascular risk. In the whole cohort (n = 90) QRISK2 (β = 0.046, p = 0.017) and FEV1 (β = -0.013, p = 0.022) were associated with PWV in multivariate analysis. The relationship between QRISK2 and PWV appeared to be modified by COPD, where the interaction term reached borderline significance (p = 0.060). FEV1 (β = 0.005, p = 0.004) was also associated with TAC in multivariate analysis. Cardiac chamber size and stroke volume was decreased in COPD compared to controls. The mean difference in left ventricle stroke volume index (LVSVI) and left and right end diastolic volume index was -10.3 ml/m<sup>2</sup> (95% CI -15.1, -5.5, p &lt; 0.001), -14.1 ml/m<sup>2</sup> (95% CI -21.9,-6.3 p &lt; 0.001) and -13.0 ml/m<sup>2</sup> (95% CI -23.3, -2.6 P &lt; 0.015) respectively, which were shown to be associated with airflow limitation in multivariate models. In the COPD group associations were found with lung hyperinflation (LVSVI: β = -0.075, p = 0.032; Left atrial size: β = -0.129, p = 0.047) and fibrinogen (TAC: β = 0.716, p = 0.030). <h3>Conclusion</h3> Surrogates for cardiovascular outcomes are adversely affected in COPD compared to a group matched for global cardiovascular risk, suggesting that current scoring systems may be suboptimal for cardiovascular risk prediction in COPD.
Diagnosis of Hirschsprung's Disease Excluded by Rectal Suction Biopsy
Authors: William O. Dobbins, Alexander H. Bill
Journal: New England Journal of Medicine (1965)

HIRSCHSPRUNG'S disease usually presents as acute or chronic colonic obstruction in infants and children.1 , 2 There is defective parasympathetic nerve supply to the rectum or rectosigmoid or, occasionally, to longer colonic segments, characterized by absence of ganglion cells and presence of hypertrophied nonmyelinated nerve fibers in the submucosal and intermuscular areas of the segments.3 4 5 This causes ineffective peristalsis and apparent narrowing of the affected segment.6 Although the clinical picture and the radiologic findings may be sufficient to suggest Hirschsprung's disease strongly it is generally considered necessary to demonstrate absence of rectal ganglion cells to establish the diagnosis.Wedge rectal biopsies containing . . .
Soundings: Anyone for tennis?
Authors: Colin Douglas
Journal: BMJ (2001)

Or would you prefer parking? Yes, I think I have a sense of the meeting. No need to go to a vote. Clearly you will be happy to go along with our administrators' plans for the once popular but now somewhat dilapidated tennis courts beyond the former nurses' home . . .

It must have happened a lot over the decades, all over the NHS. Hospital tennis—a pastime easily compatible with the kind of on-call schedules that persisted into the early 1970s—is now nothing but a vestigial memory of the nearly retired.

It was good while it lasted: for residents a seasonal bonus of the club life of the mess. Smashing tennis balls around in the sun was a sober, permissible, and welcome diversion, and still only five minutes away from the ward. For the generation before us there were hospital leagues and evening tennis parties: the stuff of Betjeman poetry and romance. Now there are only mysterious, fading white lines in crowded car parks: faint traces of a bygone culture involving strange cries, shoe whitener, and primitive wooden rackets.

In our new hospital, it is rumoured, there will be a fitness centre. Like everything else there, it will be expensive, gleamingly modern, and intricately scheduled for maximum use. Grim faced devotees will toil, alone with their suffering, in strange chrome and black devices, most of them little more than a high technology revival of the Victorian prison treadmill.

I doubt if I shall be joining them. Tennis was fun, treadmills aren't, but that's progress. Meanwhile, through the last months on our old crowded city centre site, I am consoled by owning a precious piece of paper, pale brown in colour and 7.5 cm in diameter, a privilege restricted to a few dozen of us with what are officially known as multisite and/or area-wide commitments.

On the disc stuck to the inside of my windscreen there is a faint crest but— strangely—no other hint of hospital, trust, or NHS associations. In bold print it proclaims “Tennis Court 2001,” and it more or less guarantees a space at any time on a site where parking causes at least as much grief as ever the internal market did. It is among my most prized possessions. But sometimes, on summer evenings when the car park is empty, there are faint and ghostly echoes: of a lost civilisation, of a more leisured and supportive hospital society, of tennis long ago.
Sudden Complete Thrombosis of an Aneurysm of the Abdominal Aorta
Authors: Peter J. Jannetta, Brooke Roberts
Journal: New England Journal of Medicine (1961)

THE complications of aneurysm of the abdominal aorta have frequently been discussed, but sudden occlusion has not been included among them. Spontaneous rupture into the retroperitoneal space,1 , 2 the peritoneal cavity3 or adjacent organs4 5 6 7 8 has repeatedly been seen, as has dissection, with its various complications.9 10 11 12 13 Emboli, too, are seen, but sudden total thrombosis is very rare even though it is frequently observed in peripheral aneurysms. Popliteal aneurysms are notoriously apt to thrombose, and femoral aneurysms also may suddenly occlude.14 15 16 This is not true, however, of aneurysms involving the aorta. Indeed, surgeons attempted to effect thrombosis of the aneurysm or at least . . .
Adjuvant postoperative chemotherapy for Dukes C colorectal cancer; weekly low-dose Irinotecan (CPT-11) plus oral 5-FU versus oral 5-FU only
Authors: K. Sasaki, H. Takasaka, K. Kiriyama, Y. Inafuku, T. Yabana, T. Furuhata, F. Hata, T. Katsuramaki, K. Hirata
Journal: Journal of Clinical Oncology (2004)

3735 Background: We have already reported that the weekly low dose CPT-11 + oral 5-FU is effective in the treatment of advanced colorectal carcinoma (CRC) with the minimal toxities (Sasaki, ASCO 2002). Oral 5-FU also have single agent activity in CRC. The purpose of this study was to evaluate a CPT-11 + oral 5-FU adjuvant chemotherapy and an oral 5-FU. Methods: 86 patients (pts) with Dukes C CRC were enrolled last 2 years. We randomly divided the curative operated Dukes C CRC pts following two treatment groups; low dose weekly CPT-11 plus oral 5-FU (Group A, n=39) and oral 5-FU (Group B, n=47). CPT-11 was given at a dose of 30 mg/m2 intravenously over 60 minutes every week. These patients received oral 5-FU every day. CPT-11 was given for 6 months every week and oral 5-FU for 12 months. All patients received these treatment on an out-patient clinic. Results: There were no grade 3/4 toxicities in both treatment groups. 6 pts of group A were not received CPT-11 more than 3 months because of grade 1 nausea and loss of appetite. These pts were not analyses the following survival study. The overall 1, 2 and 4 years survival rate were 100, 91 and 86% respectively in group A, 100,89 and 75% in group B (N.S.). The recurrence rate was high in the group B, but no significant difference between group A and B (24% vs 32%,). Conclusions: Further studies are necessary. But, the regimen of weekly low dose CPT-11 plus oral 5-FU in the adjuvant treatment of curative Dukes C CRC may show anti-cancer activity, and an acceptable toxicities on an out-patient treatment. No significant financial relationships to disclose.
Use of Ambulatory Electrocardiographic Monitoring to Identify High-Risk Patients with Congenital Complete Heart Block
Authors: Robert C. Dewey, Mark A. Capeless, Arthur M. Levy
Journal: New England Journal of Medicine (1987)

To define the long-term natural history of congenital complete heart block, we followed 27 patients prospectively by means of frequent ambulatory electrocardiographic (ECG) recordings for a mean (±SD) of 8±3 years. During that time, 8 of the 13 patients with a mean daytime heart rate below 50 bpm (Group A) had cardiac complications such as sudden death, syncope, presyncope, or excessive fatigue. Six of the eight patients had additional ECG findings that suggested an instability of the junctional escape mechanism. These findings included nocturnal junctional exit block (three patients), little or no change in the junctional rate with physical activity (three patients), and associated tachyarrhythmias (three patients). None of the 14 patients with a mean daytime heart rate of 50 bpm or more (Group B) had an adverse clinical outcome, and 5 of the 13 patients in Group A also remained well. Among the five patients in stable condition in Group A, three had no evidence of an unstable junctional mechanism. We conclude that patients with a mean daytime junctional rate below 50 bpm and other evidence of an unstable junctional escape mechanism should probably undergo prophylactic pacemaker implantation. Since junctional exit block and tachyarrhythmias sometimes appear first during follow-up, the method of risk stratification employed in this study depends on serial ambulatory ECG recordings. (N Engl J Med 1987; 316:835–9.)
Effects of Corticosteroid Therapy on Human Monocyte Function
Authors: John J. Rinehart, Arthur L. Sagone, Stanley P. Balcerzak, G. Adolph Ackerman, Albert F. LoBuglio
Journal: New England Journal of Medicine (1975)

Since high-dose corticosteroid therapy appears to im pair cellular defense mechanisms, this study examined its effect on human monocyte function. Fifteen normal volunteers were studied before and after a three-day course of prednisone therapy (50 mg every 12 hours for six doses). A transient period of monocytopenia occurred during the first few hours of therapy. Monocyte killing of Staphylococcus aureus was reduced in nine subjects from 5.6 ± 0.2 (± S.E.) x 106 organisms before to 1.3 ± 0.4 x 106 organisms at completion of therapy (p < 0.01). Similarly, killing of Candida tropicalis in four subjects fell from 9.3 ± 0.6 to 0.6 ± 0.3 X 106 organisms (p < 0.01). Bactericidal activity returned to normal levels 48 hours after the last dose of prednisone. These same monocyte preparations had normal or increased chemotactic response, phagocytic rate of cryptococci, hexosemonophosphate-shunt response to phagocytosis and ultrastructural characteristics. This impairment of bactericidal and fungicidal activity during prednisone therapy may contribute to the infectious complications seen in patients receiving comparable doses of corticosteroids. (N Engl J Med 292:236–241, 1975)
Combination of a Novel Oncolytic Immunotherapeutic Agent, Coxsackievirus A21 and Pd-1 Blockade Significantly Reduces Tumor Growth and Improves Survival in an Immune Competent Mouse Melanoma Model
Authors: D. Shafren, M. Quah, Y. Wong, R.H. Andtbacka, G. Au
Journal: Annals of Oncology (2014)
A New Concept of the Etiology of Megaloureters
Authors: Orvar Swenson, Edward MacMahon, William E. Jaques, James S. Campbell
Journal: New England Journal of Medicine (1952)

THE association of megalobladder and megaloureters with megacolon has been reported.1 2 3 Twenty-two of our patients with Hirschsprung's disease were studied with cystometrograms; in 12 patients the bladder capacity was considerably above normal. In 7 of these the changes were pronounced, with absence of emptying contractions in response to filling increments. Maximum distention of the bladder produced an urge to void and emptying seemed to take place because of increased intraabdominal pressure following strong voluntary contractions of the abdominal musculature. In addition to these bladder abnormalities, 3 patients with bilateral megaloureters and 1 with a unilateral megaloureter were treated in our . . .
Transdermal estrogen therapy improves cholesterol levels and lipid profiles in men with prostate cancer
Authors: J. Q. Purnell, L. B. Bland, M. Garzotto, D. Lemmon, E. M. Wersinger, C. W. Ryan, T. M. Beer
Journal: Journal of Clinical Oncology (2004)

8035 Background: Hypogonadal men have adverse changes in lipids and body composition that are reversed by testosterone replacement. Studies of testostorone replacement co-administered with aromatase inhibitors show that these benefits are in part mediated through conversion of androgens to estrogenic hormones. Lipid and body composition changes may contribute to the long-term morbidity of androgen deprivation therapy for prostate cancer (PC). Oral estrogen therapy for PC is associated with an increased risk of thromboembolic complications, but parenteral administration may be safer. As part of a study of transdermal estrogen (TDE) in androgen-independent PC (AIPC) patients, we sought to determine the impact of such therapy on serum lipids and body composition. Methods: We measured serum cholesterol, triglycerides, LDL, HDL (total, HDL2 and HDL3), VLDL-C, Apolipoprotein-B, and Lp(a) before and 8 weeks after starting TDE therapy (six 7.6 mg patches applied every 7 days) in androgen-deprived men with AIPC. We examined body composition with whole body DEXA and fat distribution with an abdominal MRI at the same time points. Results: Mean ± SD for variable that changed are shown in the table. No significant change was observed for HDL3, triglycerides, VLDL, or Lp(a). MRI data were available for 13 of these men. No change was observed in any of the body composition measures including: % fat, fat mass, lean mass, trunkal fat, intra-abdominal fat, or subcutaneous fat. Conclusions: Androgen deprived men treated with TDE had significant improvements in LDL and HDL levels without raising triglyceride levels. The observed changes are sufficiently large to have the potential to reduce cardiovascular risk. Longer-term observation is necessary to determine if improvements in body composition changes would follow. Controlled studies are needed to determine the impact of TDE therapy on cardiovascular risk. No significant financial relationships to disclose.
Problems of Ischemia of the Lower Extremity
Authors: George R. Dunlop
Journal: New England Journal of Medicine (1952)

AMONG the problems of an aging population, ischemia of the lower extremities ranks high in importance. Until recently it was thought that peripheral ischemia due to this disease was an irreversible process. Now, thanks to early investigations in this field, the value of lumbar sympathectomy has been adequately demonstrated. It is no longer justifiable to assume that a thigh amputation is the only treatment for failing circulation to the lower extremities. Linton1 has pointed out that this operation offers "the best protection that can be given the patient against the development of gangrene in old age." There are now more . . .
A large-scale multi-center independent validation study of a panel of seven biomarkers for the detection of ovarian cancer
Authors: Z. Zhang, R. C. Bast, I. Vergote, C. Høgdall, F. R. Ueland, A. Van der Zee, Z. Wang, C. Yip, D. W. Chan, E. T. Fung
Journal: Journal of Clinical Oncology (2006)

5057 Background: Previously we discovered seven serum biomarkers: ITIH4, transthyretin, ApoA1, CTAPIII, hepcidin, transferrin, and SAA, for the detection of ovarian cancer. They are fragments, cleavages, or PTMs of circulating proteins that are difficult to measure by conventional immunoassays. Using optimzed mass spectrometry assays, we evaluated these biomarkers in a large-scale multi-center study. Methods: A total of 607 serum samples from five sites were analyzed using SELDI TOF-MS protocols optimized for the seven biomarkers. They included 234 women with benign gynecologic diseases, and 373 patients with invasive epithelial ovarian cancer (101 early stage, 231 late stage, and 40 stage unknown). Among them, 165 benigns and 228 cancers had a CA125 available at time of analysis. The median and quartiles of CA125 for benign, early stage, and late or unknown stage were 26/11/57 IU, 80/22/434 IU, and 234/40/1114 IU, respectively. The biomarkers were assessed individually using the Mann-Whitney U Test. A linear composite index was derived in an unsupervised fashion using data from one site and then calculated for the remaining data using the fixed formula. ROC curve analyses were performed on data from individual sites and all sites combined. Results: All seven biomarkers individually demonstrated statistically significant differentiating power, and the majority had p-value&lt;0.00001. AUCs of the composite index in ROC analyses for the six sites were 0.602, 0.566, 0.821, 0.813, and 0.592 in detecting cancer at all stages from benign. On the combined data, the differences in AUC between the index and CA125 were not statistically significant for the detection of cancer at all stages (AUC=0.706 vs. 0.725) or early stages only (AUC=0.534 vs. 0.653). However, the index did better at the high-sensitivity range. At a fixed sensitivity of 86%, the specificity of the index was 34% (77/226) compared to CA125 at 26% (42/163). For early stage cases, at a fixed sensitivity of 84%, the specificity of the index was 24% (55/226) compared to CA125 at 14%% (22/163). Conclusions: We validated seven previously discovered biomarkers, individually and in combination. Prospective studies and assay development are under way to further characterize their clinical utility. [Table: see text]
Human Intrauterine Parabiotic Syndrome and Its Complications
Authors: Richard L. Naeye
Journal: New England Journal of Medicine (1963)

THE syndrome associated with intrauterine transfer of blood between uniovular twins has recently attracted clinical attention.1 2 3 4 5 6 7 8 9 10 As a consequence of blood transfer through anastomotic vessels in the of 2 additional pairs was also studied. Severe polyhydramnios often developed in the amniotic sac of the polycythemic twin. This led to premature delivery of at least 7 of the pairs (Table 1). Amniocentesis placenta 1 twin becomes polycythemic, and the other anemic. This feature resembles experimental parabiotic intoxication, but other features are unique because the parabiosis develops during intrauterine life. Polyhydramnios developing in the amniotic sac of the polycythemic twin often leads . . .