tbuckley/cabot-search huggingface dataset:
The association of FDG PET/CT and NaF PET/CT with survival outcomes in patients (pts) with metastatic genitourinary malignancies (mGU) treated with cabozantinib + nivolumab +/- ipilimumab (CaboNivo +/- Ipi).
Authors: Nicholas I. Simon, Katherine Lei, Nicholas Peter Verdini, Jeffrey Lin, Andy Vega, Scot Anthony Niglio, Amir Mortazavi, Sumanta K. Pal, Jeffrey Kempf, Murray Becker, Michael V. Knopp, Chadwick Wright, Alex Jung, Peter L. Choyke, Seth M. Steinberg, Esther Mena, Liza Lindenberg, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2022)

452 Background: This study determined the association of functional imaging parameters obtained on FDG PET/CT and NaF PET/CT with OS for pts with mGU malignancies treated on a phase I study with CaboNivo +/- Ipi. Methods: Pts on this phase I study underwent sequential (1-hour apart) FDG PET/CT and NaF PET/CT imaging at baseline and at first-restaging (8 weeks follow up). Scan semi-quantitative parameters measures included: maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for FDG and MTV for NaF. Total lesion number was captured for all scans. The association of imaging parameters and survival was determined with Kaplan-Meier curves. Baseline values and percent change values were calculated. Results: 81 pts were included in the analysis. 67 (83%) were males; Median age was 63 (range 25-86); Histologically, 30 pts had urothelial carcinoma, 15 clear cell renal cell carcinoma, 9 germ cell tumors, 8 urachal/adenocarcinoma, 8 prostate cancer, 3 penile cancer, 3 squamous cell carcinoma, 3 renal medullary carcinoma, and 2 small cell (1 bladder, 1 prostate). All 81 had a baseline FDG PET scan, 78 pts received baseline NaF PET scans; 66 received both FDG PET and NaF PET baseline and follow up scans. 957 total lesions were detected on FDG PET across all histologies, 87 liver (9%), 252 lung (26%), 152 bone (16%), 411 lymph node (43%), and 55 other visceral metastases (6%). 414 total lesions were detected on NaF imaging. Low vs high baseline FDG MTV (31 vs 11 months, p = 0.0002), TLG (30 vs 11 months, p = 0.0004), Lesion number (49 vs 15 months, p = 0.0005), and SUVmax (25 vs 12 months, p = 0.025), FDG lesion number decrease or no change vs increase (24 vs 12 months, p = 0.0068), and low vs high baseline NaF MTV (26 vs 16 months, p = 0.007), and lesion number (26 vs 16 months, p = 0.007) showed the strongest associations with OS. A multivariable Cox analysis demonstrated that baseline FDG MTV (HR = 2.87, 95% CI 1.62-5.08, p = 0.0003) and FDG lesion number percent change (HR = 2.71, 95% CI 1.40-5.24, p = 0.0031) were jointly associated with OS. Conclusions: Baseline functional imaging parameters and percent change seen on follow imaging with FDG PET and NaF PET are prognostic in mGU pts treated with CaboNivo +/- ipi. Additional parameters and histologic subsets will be presented.
SARS-CoV-2-specific T Cell Immunity after Vaccination with Sputnik V and BBIBP-CorV
Authors: Darya Babrukevich, N. Antonevich, Andrei Hancharou, A. Rynda, O. Timohina, Y. Minich, V. Mantivoda, Lawrence DuBuske
Journal: Journal of Allergy and Clinical Immunology (2022)
Splenectomy and Immunity
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors
Authors: Alexander Muik, Elena Garralda, Isil Altintas, Friederike Gieseke, Ravit Geva, Eytan Ben-Ami, Corinne Maurice-Dror, Emiliano Calvo, Patricia M. LoRusso, Guzman Alonso, Maria E. Rodriguez-Ruiz, Kristina B. Schoedel, Jordan M. Blum, Bianca Sänger, Theodora W. Salcedo, Saskia M. Burm, Eliana Stanganello, Dennis Verzijl, Fulvia Vascotto, Angelica Sette, Juliane Quinkhardt, Theo S. Plantinga, Aras Toker, Edward N. van den Brink, Mark Fereshteh, Mustafa Diken, David Satijn, Sebastian Kreiter, Esther C.W. Breij, Gaurav Bajaj, Eleni Lagkadinou, Kate Sasser, Özlem Türeci, Ulf Forssmann, Tahamtan Ahmadi, Uğur Şahin, Maria Jure-Kunkel, Ignacio Melero
Journal: Cancer Discovery (2022)

Abstract Checkpoint inhibitors (CPI) have revolutionized the treatment paradigm for advanced solid tumors; however, there remains an opportunity to improve response rates and outcomes. In preclinical models, 4-1BB costimulation synergizes with CPIs targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis by activating cytotoxic T-cell–mediated antitumor immunity. DuoBody-PD-L1×4-1BB (GEN1046) is an investigational, first-in-class bispecific immunotherapy agent designed to act on both pathways by combining simultaneous and complementary PD-L1 blockade and conditional 4-1BB stimulation in one molecule. GEN1046 induced T-cell proliferation, cytokine production, and antigen-specific T-cell–mediated cytotoxicity superior to clinically approved PD-(L)1 antibodies in human T-cell cultures and exerted potent antitumor activity in transplantable mouse tumor models. In dose escalation of the ongoing first-in-human study in heavily pretreated patients with advanced refractory solid tumors (NCT03917381), GEN1046 demonstrated pharmacodynamic immune effects in peripheral blood consistent with its mechanism of action, manageable safety, and early clinical activity [disease control rate: 65.6% (40/61)], including patients resistant to prior PD-(L)1 immunotherapy. Significance: DuoBody-PD-L1×4-1BB (GEN1046) is a first-in-class bispecific immunotherapy with a manageable safety profile and encouraging preclinical and early clinical activity. With its ability to confer clinical benefit in tumors typically less sensitive to CPIs, GEN1046 may fill a clinical gap in CPI-relapsed or refractory disease or as a combination therapy with CPIs. See related commentary by Li et al., p. 1184. This article is highlighted in the In This Issue feature, p. 1171
Cyclophosphamide
Authors: G. H. Fairley
Journal: BMJ (1963)

drugs.However, although it is not pos- sible to prove this the responsibility of fluothane for the jaundice seems convincing.While many drugs have been indic- ted as causes of liver damage, this patient received no other agent even suspected of hepato-toxicity.Intra-abdominal opera- tion near the liver and antibiotics have also been blamed; however, this lady was in hospital for immediate and delayed suture of her ulnar nerve, and antibiotics were not administered later than seven weeks before the onset of jaundice.
Energy expenditure with indoor exercise equipment
Authors: T. Yannios
Journal: JAMA (1996)

<h3>In Reply.</h3> —Dr Domino notes that our estimate of dietary nicotine contribution to cotinine (0.02 ng/mL) is below the limit of detection (sensitivity) of our analytical method. We agree that our estimate of dietary nicotine contribution is less than the detection limit of our method and represents a small contribution. Such an estimate can be made because we had cotinine data on thousands of persons in the regression analysis. From our Figure 2, Domino states that the maximum serum cotinine levels peak at approximately 0.1 ng/mL. The maximum is actually much greater than 0.1 ng/mL—the geometric mean we reported (Table 4) was 0.113 to 0.124 ng/mL, depending on age group. Since our study provides, to our knowledge, the only data available in the literature that relates measured levels of cotinine to dietary consumption, we thought it was important to provide an estimate of the contribution of diet to cotinine levels even though
Genital warts.
Authors: W C Stack
Journal: BMJ (1990)

SIR,-The British Thoracic Society's report for the control and prevention of tuberculosis in Britain referring to protection of NHS employees makes recommendations which have been awaited a long time.'It is generally agreed that far too many routine chest radiographs are performed on NHS employees.Yet the report suggests that grade 2 reactions to Heaf testing in the absence of previous BCG should be regarded as similar to grades 3 or 4 and that chest radiography should be performed to decide if further action is needed.I analysed the results of 1424 tuberculin tests on prospective NHS staff in 12 of the 19 districts in North Western region over three months (table).Most of those tested were young student nurses, and few had an unequivocal history of previous BCG.When these tests were carried out it was still policy to examine all staff by chest radiography and in this group no cases of tuberculosis were found.Heaf test reactions in 1424 prospective NHS staffJ in 12 districts in North Western region Heaf test grade No ('%) of staff n= 1424) 0 235 (16)
Impotence
Authors: S. L. Simpson
Journal: BMJ (1950)

BI1TJIS,RNALamphetamine and caffeine-its action is not sedative but rather the reverse.The two important advances in medical therapy, therefore, are that it is no longer necessary to procure sedation to achieve control of epilepsy, and that specificity of response is being achieved in the control of the different forms of epilepsy.Conclusion In this review I have not meant to record facts about epilepsy, old or new, but have tried to show where new knowledge seems to be leading us.Lest I seem to have integrated clinical and electroencephalographic evidence without details of the supporting data, I would urge that the E.E.G. has presented further signs, which have been used in this paper with all the other evidence to reach conclusions through the clinical method of deduction.This clinical method uses the history, the physical examination, and the results of special investigations, of which the E.E.G. is simply one.This is not belittling the E.E.G., for it has presented us with an objective method of studying cerebral activity which will continue of the first importance to the study of epilepsy.
Correction: The Promise of Prevention: The Effects of Four Preventable Risk Factors on National Life Expectancy and Life Expectancy Disparities by Race and County in the United States
Authors: Goodarz Danaei, Eric B. Rimm, Shefali Oza, Sandeep C. Kulkarni, Christopher J. L. Murray, Majid Ezzati
Journal: PLoS Medicine (2011)

Background: There has been substantial research on psychosocial and health care determinants of health disparities in the United States (US) but less on the role of modifiable risk factors.We estimated the effects of smoking, high blood pressure, elevated blood glucose, and adiposity on national life expectancy and on disparities in life expectancy and disease-specific mortality among eight subgroups of the US population (the ''Eight Americas'') defined on the basis of race and the location and socioeconomic characteristics of county of residence, in 2005. Methods and Findings:We combined data from the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System to estimate unbiased risk factor levels for the Eight Americas.We used data from the National Center for Health Statistics to estimate age-sex-disease-specific number of deaths in 2005.We used systematic reviews and meta-analyses of epidemiologic studies to obtain risk factor effect sizes for disease-specific mortality.We used epidemiologic methods for multiple risk factors to estimate the effects of current exposure to these risk factors on death rates, and life table methods to estimate effects on life expectancy.Asians had the lowest mean body mass index, fasting plasma glucose, and smoking; whites had the lowest systolic blood pressure (SBP).SBP was highest in blacks, especially in the rural South-5-7 mmHg higher than whites.The other three risk factors were highest in Western Native Americans, Southern low-income rural blacks, and/or low-income whites in Appalachia and the Mississippi Valley.Nationally, these four risk factors reduced life expectancy at birth in 2005 by an estimated 4.9 y in men and 4.1 y in women.Life expectancy effects were smallest in Asians (M, 4.1 y; F, 3.6 y) and largest in Southern rural blacks (M, 6.7 y; F, 5.7 y).Standard deviation of life expectancies in the Eight Americas would decline by 0.50 y (18%) in men and 0.45 y (21%) in women if these risks had been reduced to optimal levels.Disparities in the probabilities of dying from cardiovascular diseases and diabetes at different ages would decline by 69%-80%; the corresponding reduction for probabilities of dying from cancers would be 29%-50%.Individually, smoking and high blood pressure had the largest effect on life expectancy disparities.Conclusions: Disparities in smoking, blood pressure, blood glucose, and adiposity explain a significant proportion of disparities in mortality from cardiovascular diseases and cancers, and some of the life expectancy disparities in the US.
Abstract 17170: Sarcomere Gene Mutation Hypertrophic Cardiomyopathy Exhibits Distinct Age-Dependent Adverse Remodeling
Authors: Samat Kabani, Maryann Concannon, Sara Saberi, Sharlene Day, Adam S Helms
Journal: Circulation (2018)

Introduction: Hypertrophic cardiomyopathy (HCM) due to mutations in sarcomere genes (G+HCM) has been associated with greater risk of adverse outcomes compared to genetic-test negative HCM (G-HCM). HCM morphologic progression across the age spectrum has not been well-defined in the presence or absence of sarcomere mutations. Hypothesis: We hypothesized that G+ HCM is associated with greater adverse remodeling than G- HCM across the age spectrum of adult HCM. Methods: In a prospectively collected HCM cohort, we studied adult HCM probands who had preserved systolic function (EF &gt;50%). To ascertain morphologic differences with age, we compared the continuous variables of left atrial size/body surface area (LA/BSA) and maximum wall thickness (MWT) by echocardiogram, analyzed by age subgroup and by linear regression. Results: Of 500 HCM probands, 241 were G+ and 259 were G-. MWT was larger for all G+ compared to all G- (19.2mm +/- 6.4mm vs. 16.8mm +/- 4.7mm, p&lt;0.001). By age subgroup, MWT was larger for G+ for ages 20-40 (20.1mm vs 15.7mm, p&lt;0.001) and ages 40-60 (19.4mm vs 16.3mm, p&lt;0.001) but not different for 60+ (17.8mm vs 18.1mm, p=0.8). In linear regression by age, there was no significant change in extent of MWT with age among G+ (p=0.7). In contrast, G- patients exhibited a positive correlation of greater MWT with age (p&lt;0.001), which was significantly different than the age relationship for G+ (p=0.008). LA/BSA was larger for all G+ compared to all G- (21.9mm/m 2 +/- 3.9mm/m 2 versus 20.9mm/m 2 +/- 3.8mm/m 2 , p&lt;0.006). By age subgroup, LA/BSA was not significantly different for G+ compared to G- ages 20-40 (20.9mm/m 2 vs 19.9mm/m 2 , p=0.193) but significantly larger for ages 40-60 (21.6mm/m 2 vs 20.0mm/m 2 , p&lt;0.01) and age 60+ (24.5mm/m 2 vs 22.6mm/m 2 , p=0.02). The regression slopes were similar for G+ vs G- (0.07 mm/m 2 /yr versus 0.09mm/m 2 /yr, p=0.36) but the elevations were significantly larger for G+ (p&lt;0.0001), indicating persistently larger LA size in G+ across the age spectrum. Conclusion: LV hypertrophy extent is similar across adult age groups in G+ HCM, while hypertrophy in G- HCM is milder in age groups &lt;60 and similar to G+ HCM only at age &gt;60. Although LA dilation is progressive with age in all HCM, G+ HCM exhibits greater LA dilation across the adult age spectrum.
Survival with Cemiplimab in Recurrent Cervical Cancer
Authors: Krishnansu S. Tewari, Bradley J. Monk, Ignace Vergote, Austin Miller, Andreia C. de Melo, Hee-Seung Kim, Yong Man Kim, Alla Lisyanskaya, Vanessa Samouëlian, Domenica Lorusso, Fernanda Damian, Chih-Long Chang, Evgeniy A. Gotovkin, Shunji Takahashi, Daniella Ramone, Joanna Pikiel, Beata Maćkowiak-Matejczyk, Eva M. Guerra Alía, Nicoletta Colombo, Yulia Makarova, Danny Rischin, Stephanie Lheureux, Kosei Hasegawa, Keiichi Fujiwara, Jingjin Li, Shaheda Jamil, Vladimir Jankovic, Chieh-I Chen, Frank Seebach, David M. Weinreich, George D. Yancopoulos, Israel Lowy, Melissa Mathias, Matthew G. Fury, Ana Oaknin
Journal: New England Journal of Medicine (2022)

Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)–blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population.
The enhanced genomic 6 mA metabolism contributes to the proliferation and migration of TSCC cells
Authors: Lei Xi, Ying Yang, Ying Xu, Fangming Zhang, Jinghui Li, Xiyang Liu, Zhenxi Zhang, Quan Du
Journal: International Journal of Oral Science (2022)

In contrast to the well-established genomic 5-methylcytosine (5mC), the existence of N6-methyladenine (6 mA) in eukaryotic genomes was discovered only recently. Initial studies found that it was actively regulated in cancer cells, suggesting its involvement in the process of carcinogenesis. However, the contribution of 6 mA in tongue squamous cell carcinoma (TSCC) still remains uncharacterized. In this study, a pan-cancer type analysis was first performed, which revealed enhanced 6 mA metabolism in diverse cancer types. The study was then focused on the regulation of 6 mA metabolism, as well as its effects on TSCC cells. To these aspects, genome 6 mA level was found greatly increased in TSCC tissues and cultured cells. By knocking down 6 mA methylases N6AMT1 and METTL4, the level of genomic 6 mA was decreased in TSCC cells. This led to suppressed colony formation and cell migration. By contrast, knockdown of 6 mA demethylase ALKBH1 resulted in an increased 6 mA level, enhanced colony formation, and cell migration. Further study suggested that regulation of the NF-κB pathway might contribute to the enhanced migration of TSCC cells. Therefore, in the case of TSCC, we have shown that genomic 6 mA modification is involved in the proliferation and migration of cancer cells.
Lentigo maligna melanoma yields to radiotherapy
Authors: Milan Korcok
Journal: JAMA (1983)

Despite a widespread belief that lentigo maligna melanoma is a radioresistant tumor, therapeutic radiologists at Toronto's Princess Margaret Hospital are recording better than 90% control of this lesion using conventional orthovoltage (140 to 400 kV) techniques. Reporting this success rate at the recent meeting of the American Society of Therapeutic Radiologists in Orlando, Fla, radiation oncologist Andrew R. Harwood, MB, said that radiation therapy provides an "excellent cosmetic result" and appears to be the treatment of choice for large lesions beyond the scope of surgery. Lentigo maligna (Hutchinson's freckle), which characteristically is seen in old age as a slow-growing, pigmented facial lesion, resembles many benign epidermal lesions. Hence, the lesion frequently is not diagnosed until it is quite large, Harwood told<i>JAMA</i> Untreated, one third to one half of such growths will progress to dermal invasion or lentigo maligna melanoma, and 10% of these invasive tumors will develop regional or
Royal twins.
Authors: J Dewhurst
Journal: BMJ (1983)

Twins occur in Britain roughly once in 80 pregnancies, and in royal circles their frequency has been of this order.An estimate of the number of pregnancies to women who were, or who became, Queens or Queen Consorts of England from '066 to the present day is about 160; two twin preg- nancies probably occurred, one to the Princess of Denmark, later Queen Anne, and one to the Duchess of Clarence, later Queen Adelaide.In Scotland the expected frequency has been somewhat exceeded: there were probably fewer than 100 royal pregnancies between the uniting of the four Scottish kingdoms under Duncan I in 1034 and the end of the reign of James VI in 1625, but these also yielded two twin pregnancies-to Joan Beaufort, wife of James I, and to Mary Queen of Scots.Even given the increased fetal and neonatal mortality of twins, the outcome of these pregnancies has been unusually poor.Queen Anne, attributed to M Dahl (left) and by the studio of J Closterman (right).Anne, Princess of
Death certificates.
Authors: M. Macleod
Journal: BMJ (1969)

have admitted that it actually gives them a " buzz " (addict jargon; positive pleasure response to some drugs, particularly morphine derivatives).This preference for meth- aqualone over barbiturates and other hypnotics shown by the young heroin addict could be ominous.It may be wise, therefore, for practitioners to prescribe this powerful hypnotic less routinely and to keep a closer watch on those patients in whom they considered its use is indicated.-Iam, etc.,
135. Sequence-Engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals
Authors: Andreas Thess, Stefanie Grund, Barbara L. Mui, Michael J. Hope, Patrick Baumhof, Mariola Fotin-Mleczek, Thomas Schlake
Journal: Molecular Therapy (2015)

Being a transient carrier of genetic information, mRNA could be a versatile, flexible and safe means for protein therapies. While recent findings highlight the enormous therapeutic potential of mRNA, evidence that mRNA-based protein therapies are feasible beyond small animals such as mice is still lacking. Previous studies imply that mRNA therapeutics require chemical nucleoside modifications to obtain sufficient protein expression and avoid activation of the innate immune system. Here, by applying sequence-engineered mRNA we show that chemically unmodified mRNA can achieve those goals as well. Using erythropoietin (EPO) driven production of red blood cells as the biological model, engineered Epo mRNA elicited meaningful physiological responses from mice to non-human primates. Even in pigs of about 20 kg in weight, a single adequate dose of engineered mRNA encapsulated in lipid nanoparticles (LNPs) induced high systemic Epo levels and strong physiological effects (Fig.). Our results demonstrate that sequence-engineered mRNA has the potential to revolutionize human protein therapies.
Contact tracing to control the spread of HIV
Authors: T. M. Vernon
Journal: JAMA (1988)

<h3>In Reply. —</h3> We appreciate the supportive words of Drs Vernon and Hoffman. Their experience in Colorado stands as a model for public health units nationwide to follow in developing programs of HIV contact tracing and partner notification. We share with them some concerns about the comments and tone of the editorial by Drs Rutherford and Woo. In addition to the several issues discussed by Drs Vernon and Hoffman, we were especially surprised that the editorial seemed to dismiss HIV contact tracing/ partner notification as a tool of limited utility, only applicable in occasional situations and scattered geographic areas. This pessimistic view of contact tracing/partner notification in HIV control is not new. Actual data, however, now collected in various states, suggest that this public health approach has usefulness that extends much beyond the narrow limits predicted by the editorial. In view of such data, we believe that public health professionals