tbuckley/cabot-search huggingface dataset:
Novel predictive biomarkers of response to immune checkpoint blockade with nivolumab ± ipilimumab in the TITAN-RCC phase 2 trial.
Authors: Marc-Oliver Grimm, Miriam Kesselmeier, Katharina Leucht, Ulrike Schumacher, Antje Tunger, Nadja Röber, Karsten Conrad, Ulrich Sommer, Gustavo Bruno Baretton, André Scherag, Laurence Albiges, Emilio Esteban, Philippe Barthélémy, Manuela Schmidinger, Jonas Busch, Begoña Pérez-Valderrama, Guillermo de Velasco, Ignacio Duran, Marc Schmitz, Rebekka Wehner
Journal: Journal of Clinical Oncology (2022)

367 Background: Despite promising therapeutic efficacy of immune checkpoint inhibitors in renal cell carcionoma (RCC) response varies significantly between individual patients. Therefore, predictors of response are urgently needed. To identify novel predictive biomarkers, we explored the characteristics of blood-circulating immune cell subsets within the population of the TITAN-RCC trial (NCT02917772) applying a tailored approach with nivolumab (nivo) and ipilimumab (ipi). Methods: In TITAN-RCC, patients with intermediate and poor risk advanced clear cell RCC started nivo Q2W induction. Upon early progressive disease (PD, week 8) or non-response (stable disease or PD) at week 16, patients received 2-4 nivo+ipi “boost” cycles. Responders (complete or partial response) to nivo induction continued with maintenance but could receive nivo+ipi for later PD. Blood samples for biomarker analyses were taken at baseline, during nivo induction and nivo+ipi “boost” cycles. Samples from 198 RCC patients (105 first line, 93 second line) were analyzed by multi-parametric flow cytometry for frequency and phenotype of T cell, monocyte, myeloid-derived suppressor cell (MDSC) and dendritic cell (DC) subsets. Baseline data were associated to response upon nivo induction and data from samples taken prior to first “boost” to response to nivo+ipi. We applied uni- and multivariable logistic regression modelling to investigate the association between treatment response and immune parameters. Here we report on single marker models (adjusted for age and gender). Results: Higher percentages of blood-circulating 4-1BB+ CD4+ T cells (adjusted odds ratio (OR adj ) 1.05, 95% CI 1.02-1.08), 4-1BB+ CD8+ T cells (OR adj 1.03, 95% CI 1.01-1.07) and LAG3+ CD4+ T cells (OR adj 1.03, 95% CI 1.01-1.05) were found in responders to nivo induction compared to non-responders. Moreover, in patients receiving nivo+ipi “boosts”, a higher proportion of PD-L1+ CD14+ monocytes (OR adj 1.22, 95% CI 1.06-1.58), PD-L1+ early-stage MDSC (OR adj 1.14, 95% CI 1.02-1.41) and PD-L1+ plasmacytoid DC (OR adj 1.08, 95% CI 1.01-1.17) was observed in responders compared to non-responders. Conclusions: We identified various immune cell-related parameters that are associated with increased or poor therapeutic efficacy in RCC patients which are currently investigated in multi-marker models. These parameters may represent novel predictive biomarkers for response to nivo±ipi in clear cell RCC. Clinical trial information: NCT02917772.
The lexicon of PET/CT reports in prostate patients: Evaluating confidence.
Authors: Jessica Baumgartner, Jonathan David Tward
Journal: Journal of Clinical Oncology (2022)

232 Background: Pet/CT scans are increasingly used to evaluate prostate cancer patients with biochemical failure following surgery or radiation therapy for localized prostate cancer. We assessed the language used in report impressions to characterize the reader's confidence for lesions in various anatomic sites. Methods: Between 2015 and 2021, 419 fluciclovine PET/CT scan reports were identified in our institutional outcomes database. Thirteen phrases routinely used in the report impression section by radiologists at least once to characterize a lesion of interest were identified. The phrases were categorized in the following confidence categories: Definitive (positive, negative), Likely (consistent with, most likely, favors, probable), and Unsure (suspicious for, concerning for, non-specific, conspicuous, compatible with, borderline, unknown). The final analysis set included 353 reports where the prescan PSA value was known within the prior 90 days of the scan. Descriptive statistics, stratified by prescan PSA value, were used to characterize this language for the following anatomic regions: bone, regional lymph nodes, prostate fossa, prostate gland/seminal vesicles, other soft tissue. Results: Overall, definitive language was used between 34.6% to 87.1% of the time, depending on the anatomic context (table). The intact prostate was the least likely site to use definitive language (34.6%), whereas bone was most likely (87.1%). Intact prostates in post-radiation patients had the most uncertainty to the persistence of disease (42.3% unsure, 23.1% likely). The highest degree of definitive certainty occurred in impressions of persons with PSA &lt;0.5 (89.2%), whereas the least definitive certainty was in patients with PSA &gt;1 (66.2%). Overall, definitive, likely and unsure findings were reported in 68.6, 9.7%, and 21.7% of scans. Conclusions: Fluciclovine PET/CT scans routinely result in equivocal findings, which vary by anatomic site of interest and prescan PSA level. The language utilized in these reports has not been standardized. Future work aims to create a clear confidence level lexicon standard to assist radiologists and providers in reporting standardization.[Table: see text]
Randomized phase II trial of neoadjuvant abiraterone plus or minus cabazitaxel in high-risk prostate cancer: ACDC-RP.
Authors: Neil E. Fleshner, Aaron Richard Hansen, Joseph Chin, Eric Winquist, Theodorus Van Der Kwast, Katherine Lajkosz, Miran Kenk, Doron Berlin, Rosette Veloso, Srikala S. Sridhar, Robert James Hamilton, Girish S. Kulkarni, Antonio Finelli, Alexandre R. Zlotta, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2022)

224 Background: High-risk prostate cancer has a significant risk of recurrence when treated with unimodal therapy. The utility of neoadjuvant therapy prior to radical prostatectomy (RP) has yet to be defined. The ACDC-RP study investigated the use of abiraterone acetate (AA) + prednisone (P) + leuprolide (LHRH) with or without cabazitaxel prior to RP in high-risk patients. Methods: This phase II trial randomized patients to Arm A (AA/P + LHRH + cabazitaxel 20 mg/m 2 with peg-filgrastim 6 cycles) or Arm B (AA/P + LHRH) for 6 months prior to RP. The primary objective was to compare the rate of pathological complete response (CR) or minimal residual disease (MRD) between treatment arms. MRD was defined as ≤5% of prostate volume involved by tumor. We present RP pathological outcomes, safety signals, and early biochemical response data. Results: Out of 78 randomized participants, 70 completed the full course of study treatment and underwent RP. Across both treatment arms, 31 (44%) men achieved either CR or MRD; 5 men had CR (2 in Arm A) and an additional 26 men exhibited MRD (15 in Arm A), p = 1 between Arm A and B. Kaplan-Meier analysis demonstrated no difference in biochemical-free survival (BFS) rate between the two treatment groups. Patients who achieved a CR/MRD experienced significantly longer BFS. Conclusions: Study findings indicate significant tumor response with 44% of patients exhibiting CR/MRD, with no significant difference observed between the two treatment arms. Patients who exhibit CR/MRD experienced better BFS rates. Genomic efforts are underway to determine predictors of response. Clinical trial information: NCT02543255. [Table: see text]
Multiple parathyroid adenomas
Authors: W. D. Schwindt
Journal: JAMA (1967)

OCCASIONALLY, two parathyroid adenomas are found in a single patient; however, the occurrence of three true adenomas is exceedingly unusual. When more than one adenoma is encountered, the possibility of parathyroid hyperplasia should be considered. This is a report of a patient in whom three parathyroid adenomas were identified and removed and a normal appearing fourth parathyroid gland identified and biopsied. <h3>Report of a Case</h3> A 37-year-old housewife had the sudden onset of acute lower abdominal pain on March 26, 1965. This pain was associated with some left shoulder pain which was accentuated with respiration. The patient was hospitalized in her hometown with the diagnosis of possible ruptured ovarian cyst. Following admission to her local hospital, she became febrile and a pleural effusion on the left was noted, and therefore she was transferred to the University Hospitals on April 4, 1965, with a diagnosis of possible pneumonia. Admission roentgenograms of
Phase II Study of Neoadjuvant Nivolumab in Patients with Locally Advanced Clear Cell Renal Cell Carcinoma Undergoing Nephrectomy
Authors: Maria I. Carlo, Kyrollis Attalla, Yousef Mazaheri, Sounak Gupta, Onur Yildirim, Samuel J. Murray, Devyn T. Coskey, Ritesh Kotecha, Chung-Han Lee, Darren R. Feldman, Paul Russo, Sujata Patil, Robert J. Motzer, Jonathan A. Coleman, Jeremy C. Durack, Ying-Bei Chen, Oguz Akin, A. Ari Hakimi, Martin H. Voss
Journal: European Urology (2022)
TCT-234 Is Final Kissing Ballooning Mandatory in the Treatment of Distal Left Main Disease Treated by Simple Cross Over Stenting?
Authors: Seung-Jung Park, Jung-Min Ahn, Hee-Soon Park, Sang Soo Cheon, Min Su Kim, Jae Hyung Roh, Hyun Woo Park, Mineok Chang, Sung-Han Yoon, Jong-Young Lee, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park
Journal: Journal of the American College of Cardiology (2014)
Illustrated Catalogue of Batteries and Electro-therapeutic Appliances.
Journal: JAMA (1897)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
State Medical Election
Journal: JAMA (1949)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
PERILS OF THE LABORATORY.
Journal: JAMA (1895)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Biosynthesis of rumbrins and inspiration for discovery of HIV inhibitors
Authors: Beifen Zhong, Jun Wan, Changhui Shang, Jiajia Wen, Yujia Wang, Jian Bai, Shan Cen, Youcai Hu
Journal: Acta Pharmaceutica Sinica B (2022)

Investigation on how nature produces natural compounds with chemical and biological diversity at the genetic level offers inspiration for the discovery of new natural products and even their biological targets. The polyketide rumbrin (1) is a lipid peroxide production and calcium accumulation inhibitor, which contains a chlorinated pyrrole moiety that is a rare chemical feature in fungal natural products. Here, we identify the biosynthetic gene cluster (BGC) rum of 1 and its isomer 12E-rumbrin (2) from Auxarthron umbrinum DSM3193, and elucidate their biosynthetic pathway based on heterologous expression, chemical complementation, and isotopic labeling. We show that rumbrins are assembled by a highly reducing polyketide synthase (HRPKS) that uniquely incorporates a proline-derived pyrrolyl-CoA starer unit, and followed by methylation and chlorination. Sequent precursor-directed biosynthesis was able to yield a group of rumbrin analogues. Remarkably, inspired by the presence of a human immunodeficiency virus (HIV)-Nef-associated gene in the rum cluster, we predicted and pharmacologically demonstrated rumbrins as potent inhibitors of HIV at the nanomolar level. This work enriches the recognition of unconventional starter units of fungal PKSs and provides a new strategy for genome mining-guided drug discovery.
Clonal lineage tracing reveals shared origin of conventional and plasmacytoid dendritic cells
Authors: Jue Feng, Joseph N Pucella, Geunhyo Jang, Marcela Alcántara-Hernández, Samik Upadhaya, Nicholas M Adams, Alireza Khodadadi-Jamayran, Colleen M Lau, Marlon Stoeckius, Stephanie Hao, Peter Smibert, Aristotelis Tsirigos, Juliana Idoyaga, Boris Reizis
Journal: Immunity (2022)
Postcoital contraception.
Authors: H C McLaren
Journal: BMJ (1977)

My colleague Dr. C.L. Brewer (January 15, p. 169) is within his rights to ask for a precise definition of abortion and contraception. I define abortion as the deliberate destruction of the embryo once it is embedded in the uterus. The absolutist on the abortion issue, until he is sure that an IUD never works by destroying an embedded embryo, must logically eschew this technique, advising his patient as to his ethical objections. She may then seek other advice once she has the facts. However, to insist that those who advise an IUD with the motive of contraception cannot herefore object to, say, intrauterine saline aimed at the destruction of a moving 27-week fetus is, in my view, stretching his argument. With further stretching it could be carried to absurdity in the rubella-early pregnancy dilemma: why not deliver the child, examine it carefully, and then if imperfect kill it with a silver hammer? Unthinkable, even if logical. Still, Dr. Brewer has a point and (with me) no doubt he will sympathize with Pope John and his advisers in their support for family spacing only by the avoidance of the fertile days - esthetically admirable but, alas, not always effective. How absurd the Catholic Church would now look if 10 years ago it had blessed the IUD only to find that it may operate not only by preventing the embedding of the zygot but by destroying it in situ - by definition an abortion. The future may settle the debate with hormones which convert the endometrium to a nonreceptive state so that a fetus is never embedded in the womb. Even better, we may develop a male hormone which prevents sperm from penetrating the ovum. Meantime, motive is important: contraception is not abortion and our abortionists should not dress up as delayed contraceptors. (Editor's note: This correspondence is now closed.)
Abstract 17332: Endothelial-Specific Deletion of Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) Leads to Microvascular Barrier Dysfunction and Cardiomyopathy
Authors: Maura Knapp, Mei Zheng, Alik Stikov, Nikola Sladojevic, Anna Chen, Konstantin G Birukov, Qiong Zhao, Amit Patel, James K Liao, Rongxue Wu
Journal: Circulation (2018)

Introduction: Cardiac microvascular hyperpermeability is a key contributor to heart disease in patients with diabetes. Although the link between diabetes and microvascular barrier dysfunction is largely unknown, expression of the transcription factor aryl hydrocarbon receptor nuclear translocator (ARNT) is significantly downregulated in the cardiac microvascular endothelial cells (CMECs) of both diabetic mouse hearts (n=5, p&lt;0.01) and the explanted hearts of patients with diabetes mellitus (n=3, p&lt;0.05). We hypothesize that cardiac microvascular permeability is limited by the expression of ARNT in the endothelium and, consequently that endothelial-cell ARNT (ecARNT) expression is essential for normal cardiac function. Methods and Results: We have recently generated tamoxifen-inducible, endothelial-cell-specific, VE-cadherin-Cre ETR2 ARNT-knockout mice (ecARNT -/- mice). ecARNT deletion is achieved by tamoxifen oral administration for two weeks. Littermates controls are either mice without tamoxifen chow or ARNT flox/flox treated with tamoxifen diet. Induction of the ecARNT -/- mutation led to vascular leakage (as determined via in-vivo endothelial permeability assay) (n=5, p&lt;0.05), which occurred predominantly in the heart, and to increases in matrix metalloproteinase (MMP) expression (microarray analysis), including a 3.8-fold increase in the expression of MMP3 (n=3, p&lt;0.01). Furthermore, MMP3 inhibition attenuated the increase in cell permeability observed in CMECs from ecARNT -/- mouse hearts (as measured via electrical cell-substrate impedance sensing), as well as cardiac vascular leakage in ecARNT -/- mice, while long-term studies indicated that ejection fractions were significantly lower (ecARNT -/- : 22.3±2.6%, Control: 33.2±1.8%;), and Left ventricular end-diastolic diameters were significantly greater (ecARNT -/- : 4.8±0.8 mm, Control: 3.6±0.6 mm; n=8,p&lt;0.01) six months after ecARNT deletion (echocardiography). Conclusion: ARNT-mediated MMP3 downregulation is required for maintaining cardiac microvascular barrier integrity and preserving cardiac function; thus, modulation of the ARNT/MMP3 axis could be a novel approach for the treatment of cardiovascular diseases such as diabetic cardiomyopathy.
Lactulose.
Authors: S G Elkington
Journal: Gut (1970)

Progress report LactuloseLactulose is a synthetic disaccharide comprising galactose and fructose in combination as 1,4-beta-galactosido-fructose.It is prepared from lactose and supplied for clinical use as a flavoured syrup* containing approximately 50 % lactulose, together with smaller amounts of galactose and of unchanged lactose (about 7 g of each per 100 ml).The intestinal mucosa possesses no disaccharidase capable of splitting lactulose into its component monosaccharides1, and only insignificant amounts are absorbed unchanged2.On reaching the colon, however, this sugar is metabolized by bacterial enzymes into carbon dioxide and low molecular weight acids (chiefly lactic and acetic)2 3. Thus in sufficient dosage lactulose lowers the faecal pH, and produces an osmotic and fermentative diarrhoea analogous to that observed in lactase-deficient subjects following the oral administration of lactose4 5.Clinical interest in lactulose first arose when Petuelyfi induced an increase in the faecal population of Lactobacillus bifidus by the administration of this sugar to adults and to bottle-fed infants.He postulated that this effect might prevent enteritis during broad-spectrum antibiotic therapy, and showed that lactulose could also be employed to treat chronic constipation4.Lactulose has been studied as a laxative in a double-blind controlled trial and has been found effective7.However, at present it appears to possess no significant advantages as an aperient over cheaper alternatives, and has therefore not achieved general acceptance for this purpose8.A novel and ingenious therapeutic concept was introduced by Bircher and his colleagues9, namely, the use of lactulose to control chronic portal-systemic encephalopathy.The rationale of this form of treatment was credited by Bircher'0 to Ingelfinger"l who had suggested that since lactulose produced an increase in colonic lactobacilli (which lack urease and other ammonia- generating enzymes' 2"12'13), there might in theory be a beneficial action in chronic portal systemic encephalopathy.In this disabling complication of advanced cirrhosis, nitrogenous substances, formed in the colon by bacterial action on protein, bypass the liver through natural or surgically formed -vascular shunts and affect the brain'4.Conventional therapy has hitherto required dietary protein restriction, purgation, and the administration of a broad-spectrum antibiotic, each of which has disadvantages.Prolonged dietary protein restriction is inconvenient and may be harmful; vigorous evacuation of the bowel by purgation or enemas may produce or exacerbate electrolyte disturbance'5.Continuous administration of a broad-spectrum antibiotic such as ncomycin may result in moniliasis, staphylococcal entero- colitis, or malabsorption of both sugars and fat'6" 7"18 9. Other measures less frequently employed include the oral administration of cultures of Lacto- bacillus acidophilus'3, which involves the consumption of large quantities of protein, and surgical exclusion of the colon20 21, which carries a considerable *'Duphalac', Duphar Laboratories Ltd.
Correction: Quantitative distribution of patient-derived leukemia clones in murine xenografts revealed by cellular barcodes
Authors: Sabrina Jacobs, Albertina Ausema, Erik Zwart, Ellen Weersing, Maaike J. Kingma, Yasmine A. S. El Menshawi, Gerald de Haan, Leonid V. Bystrykh, Mirjam E. Belderbos
Journal: Leukemia (2020)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.