tbuckley/cabot-search huggingface dataset:
Comprehensive genomic profiling (CGP) of chromophobe renal cell carcinoma (chrRCC) compared with clear cell RCC (ccRCC): Impact of <i>FLCN</i> genomic alteration (GA) status.
Authors: Gennady Bratslavsky, Andrea Necchi, Philippe E. Spiess, Petros Grivas, Joseph M Jacob, Oleksandr Kravtsov, Richard S.P. Huang, Vamsi Parini, Brennan Decker, Douglas I. Lin, Dean C. Pavlick, Natalie Danziger, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2022)

292 Background: FLCN is a tumor suppressor gene associated with cutaneous hair follicle development. FLCN germline mutations are linked to inherited chrRCC in the Birt-Hogg-Dube (BHD) syndrome. We queried whether clinically sporadic chrRCC featured FLCN mutations by comparing the genomic profiles of chrRCC with ccRCC. Methods: 108 chrRCC and 2110 ccRCC underwent hybrid-capture based comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: Patients (pts) with chrRCC were more frequently female and younger than pts with ccRCC p &lt;.0001). None of the submitted clinical records in the chrRCC cases listed signs of BHD syndrome. FLCN GA were identified in only 2.3% of the ccRCC cases with 37% of the GA predicted to be germline. chrRCC did not reveal somatic or germline FLCN GA. GA/tumor were slightly higher in ccRCC vs chrRCC (3.6 vs 2.4; NS). GA more frequent in chrRCC included TP53, RB1 and PTEN. GA more frequent in the ccRCC included VHL, BAP1, PBRM1, SETD2, CDKN2A/B, ARID1A, NF2, PIK3CA and TERT. Putative biomarkers of immune checkpoint inhibitor (ICPI) response were infrequent in both groups with only a slightly higher, but still low, mean TMB in ccRCC vs chrRCC cases. IHC revealed moderate PD-L1 expression at low and minimal PD-L1 expression at high staining level, which was slightly increased in the chrRCC group. Conclusions: FLCN mutations that are associated with the familial incidence of chrRCC were not associated with sporadic chrRCC. Sporadic chrRCC has substantially different genomic profile from ccRCC and may harbor a few ‘targetable’ GA. The prediction of response to ICPI in RCC remains challenging with chrRCC featuring slightly higher PD-L1 expression and ccRCC featuring higher PBRM1 GA and higher TMB.[Table: see text]
BACTERIOPHAGE THERAPY
Journal: JAMA (1933)

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
Effect of neoadjuvant chemotherapy (NAC) on patient preferences for adjuvant treatment in muscle-invasive urothelial carcinoma (MIUC): A multi-country discrete choice experiment (DCE).
Authors: Edward I Broughton, Gary D. Steinberg, Michael Roger Harrison, Julia Braverman, Dena H. Jaffe, Oliver Will, Steven S. Senglaub, Kristen King-Concialdi, Kathleen Beusterien
Journal: Journal of Clinical Oncology (2022)

454 Background: Patient preference is an important factor in selecting appropriate treatment choices. Although underutilized, the standard of care for MIUC is with NAC, whereas evidence for adjuvant therapy is less clear. With the introduction of novel adjuvant treatments such as immune checkpoint inhibitors, treatment options are expected to expand. This study examines whether preferences for adjuvant therapy is impacted in MIUC patients receiving NAC. Methods: A cross-sectional, web-based survey included patients ≥ 18 years old who self-reported being diagnosed with MIUC and underwent radical cystectomy or nephroureterectomy without recurrence. Patients were recruited from the US, UK, Canada, France, and Germany (May–Sep 2021). A DCE using 2 adjuvant treatment profiles included 8 attributes: cancer-free survival, overall survival (OS), hypothyroidism requiring life-long hormone therapy, risk of a serious adverse event (requiring medical intervention/possible hospitalization), nausea, fatigue, diarrhea, and a dosing regimen (frequency of treatment and monitoring); an opt-out option of no treatment was also shown. Patients were grouped according to self-reported receipt of NAC. Descriptive statistics and hierarchical Bayesian logistic model with estimated preference weights were used. Relative importance estimates (mean ± standard error), or how much the attribute ranges accounted for the variation in preferences, were computed for each attribute. Bivariate comparisons used t-tests. Results: This interim analysis identified 205 patients (70.7% of target sample; US, n = 99; Germany, n = 60; UK, n = 31; Canada, n = 14; France, n = 1). Of 82 patients (40.0%) receiving NAC, 32.7% were patients &gt; 65 years and 55.1% were male; receipt of NAC did not differ by age ( P = 0.248) or sex ( P = 0.731). Patients were willing to accept increased risk in toxicities for increased treatment efficacy. Specifically, mean relative importance of treatment attributes showed that difference in median OS (25 months compared to 78 months) was most important (34.6% ± 1.6), although less so for those who did not receive NAC (30.2% ± 2.4 vs 37.5% ± 2.0; P = 0.022). Patients chose an adjuvant treatment option over ‘no treatment’ 91% of the time, with similar findings by NAC status. Conclusions: Preliminary data indicates that receipt of NAC impacts preferences for adjuvant treatment attributes. However, regardless of these attributes, patients still preferred adjuvant treatment over none. These results suggest that providing standard of care NAC does not reduce patient preference for adjuvant therapy; rather, patient preferences for adjuvant treatment attributes vary by treatment history, with implications for improving quality of care and outcomes.
Retraction: UM-164: A Potent c-Src/p38 Kinase Inhibitor with <i>In Vivo</i> Activity against Triple-Negative Breast Cancer
Authors: Rabia A. Gilani, Sameer Phadke, Li Wei Bao, Eric J. Lachacz, Michele L. Dziubinski, Kristoffer R. Brandvold, Michael E. Steffey, Frank E. Kwarcinski, Carrie R. Graveel, Kelley M. Kidwell, Sofia D. Merajver, Matthew B. Soellner
Journal: Clinical Cancer Research (2020)

[This article][1] ([1][2]) has been retracted at the request of the authors. During their efforts to advance related compounds and analogues, the authors were not able to reproduce the in vivo efficacy results represented in Fig. 5. The authors apologize to the scientific community and deeply regret
Issue Information
Authors: Carlo Brugnara, Stephen Ansell, Barbara Bain, Olivier Bernard, Anna Falanga, Shaji Kumar, Elizabeth Nemeth, David Porter, Ayalew Tefferi, Angela Weyand, Maureeen Achebe, Natasha Archer, Michael Auerbach, Pablo Bartolucci, Amy Bei, Joel Bennett, Ananda Prasad, Michelle Bayman, John Wiley, Joe Tomaszewski, Sheeba Martin, C Printers, Pte Ltd, San Parul Bhargava, Giada Francisco, Alessandra Biffi, Gautam Borthakur, Elisa Houston, Oh Cincinnati, Dario Bunn, Jorge Castillo, Daniela Cilloni, Jorge Cortes, Stacy Croteau, Corey Cutler, Lydie Da Costa, Paola Dal Cin, Courtney Boston, Houston Dinardo, Manoj Duraisingh, Elihu Estey, Guido Finazzi, Robert Fleming, Lucia Louis, Angela Dispenzieri, Deborah Elstein, Israel Jerusalem, Robert Boston, Letizia Louis, Paolo Foroni, Noelle Fortina, Peter Gaines, Frederic Galacteros, Patrick Gallagher, Guillermo Garcia-Manero, Beatrice Gee, Atlanta Ga, Saghi Ghaffari, New York, Mark Gladwin, Ivana Gojo, Jason Gotlib, Rachael Stanford, Jose Halperin, Jane Hankins, Elizabeth Hexner, John Higgins, Achille Iolascon, Elias Jabbour, Judith Houston, Eirini Karp, M Klimek, Marina Konopleva, Mark Houston, Robert Koury, Martha Lacy, Wilbur Lam, Francesco Lanza, Sophie Lanzkron, Mark Litzow, Alison Loren, Chris Lowrey, Franco Locatelli, Naomi Luban, Elisabet Manasanch, Mary Martin, Peter Marks, Anthony Mato, Janice Mcfarland, Christine Mclaren, Marc Michel, Caterina Minniti, Ann Mullally, Rakhi Naik, Valentina Nardi, Donna Neuberg, Ellis Boston, Bian Siok, Singapore Ng, Luigi Notarangelo, Enrico Novelli, Julie Panepinto, Animesh Pardanani, Melanie Percy, Alexander Perl, Elisa Piva, Olga Pozdnyakova, Rajiv Boston, Raffaele Pruthi, Linda Resar, Ran Reshef, Jean-Antoine Ribeil, Alicia Boston, Gail Rivera, New Roboz, Marco Ruggeri, Elisa Rumi, Vijay Sankaran, Giorgia Boston, Jodi Scapin, Dhvanit Segal, Akiko Shah, Amy Shimamura, Merav Sobota, Aliyah Socolovski, Martha Sohani, Martin Boston, Richard Steinberg, Jakub Stone, Marilyn Svoboda, Alberto Telen, Vicenza Tosetto, Italy Swee, Lay Thein, Venee Tubman, Lynne Houston, Celalettin Uhl, Srdan Ustun, Katja Houston, Stanford Weinacht, Olga Weinberg, Connie Westhoff, Clive Zent, Koji Sasaki, Nicholas Short, Nitin Jain, Farhad Ravandi, Ching-Hon Pui, Hagop Kantarjian, Rafał Mazgaj, Paweł Lipiński, Eunice Sindhuvi, Edison Aleksandra, Shuangyou Liu, Biping Deng, Zhichao Yin, Yuehui Lin, Lihong An, Dan Liu, Jing Pan, Xinjian Yu
Journal: American Journal of Hematology (2021)

10,651 (The Americas), US$11,067 (Rest of World), €7,145(Europe), £5,652 (UK).Prices are exclusive of tax.Asia-Pacific GST,
Linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease
Authors: Arunabh Sharma, Silke Szymczak, Malte Rühlemann, Sandra Freitag-Wolf, Carolin Knecht, Janna Enderle, Stefan Schreiber, Andre Franke, Wolfgang Lieb, Michael Krawczak, Astrid Dempfle
Journal: Gut Microbes (2022)

Dysbiosis of the gut microbiome is a hallmark of inflammatory bowel disease (IBD) and both, IBD risk and microbiome composition, have been found to be associated with genetic variation. Using data from families of IBD patients, we examined the association between genetic and microbiome similarity in a specific IBD context, followed by a genome-wide quantitative trait locus (QTL) linkage analysis of various microbiome traits using the same data. SNP genotypes as well as gut microbiome and phenotype data were obtained from the Kiel IBD family cohort (IBD-KC). The IBD-KC is an ongoing prospective study in Germany currently comprising 256 families with 455 IBD patients and 575 first- and second-degree relatives. Initially focusing upon known IBD risk loci, we noted a statistically significant (FDR<0.05) association between genetic similarity at SNP rs11741861 and overall microbiome dissimilarity among pairs of relatives discordant for IBD. In a genome-wide QTL analysis, 12 chromosomal regions were found to be linked to the abundance of one of seven microbial genera, namely Barnesiella (chromosome 4, region spanning 10.34 cM), Clostridium_XIVa (chr4, 3.86 cM; chr14, two regions spanning 7.05 and 13.02 cM respectively), Pseudoflavonifractor (chr7, 12.80 cM) Parasutterella (chr14, 8.26 cM), Ruminococcus (chr16, two overlapping regions spanning 8.01 and 16.87 cM, respectively), Roseburia (chr19, 7.99 cM), and Odoribacter (chr22, three regions spanning 0.89, 5.57 and 1.71 cM, respectively), as well as the Shannon index of α diversity (chr3, 1.47 cM). Our study thus shows that, in families of IBD patients, pairwise genetic similarity for at least one IBD risk locus is associated with overall microbiome dissimilarity among discordant pairs of relatives, and that hitherto unknown genetic modifiers of microbiome traits are located in at least 12 human genomic regions.
Errata: State of research: environmental pathways and food chain transfer
Journal: Environmental Health Perspectives (1984)

On page 267, column 1, lines 22-23, the sentence, "Of the mouse hepatocarcinogens, only 4-methoxy-1,3-phenylenediamine was also carcinogenic for other sites (i.e., hematopoietic system)' should be omitted.Also, on page 262, column 1, under 'Amount of Dosing," the units should be mg/kg diet, not ppm/day.
Risk of secondary malignancies after pelvic radiation: A population-based analysis.
Authors: Andrew Salib, Connor McPartland, James Ryan Mark, Costas D. Lallas, Edouard John Trabulsi, Leonard G. Gomella, Thenappan Chandrasekar
Journal: Journal of Clinical Oncology (2022)

478 Background: Radiation therapy (RT) is an integral component of the multimodal therapy of pelvic malignancies, either as primary treatment or in combination with surgical resection. In addition to local treatment effects on nearby pelvic organs, RT has been established to be a risk factor for delayed secondary malignancies. In this study, we examine the rate of any secondary malignancies following RT for primary pelvic malignancies, with a specific emphasis on secondary pelvic malignancies Methods: Using the SEER (Surveillance, Epidemiology, and Ends Results) database, we retrospectively examined 2,102,192 patients with primary pelvic malignancies (prostate, bladder, uterine, rectal, cervical). For each disease site, we compared the rate of all secondary malignancies in radiated patients to non-radiated patients. Secondary malignancies were then stratified as pelvic and non-pelvic, in order to determine the local effect of RT on malignancy risk. Results: A total of 2,102,192 patients were examined (1,189,108 prostate, 315,026 bladder, 88,809 cervical, 249,535 uterine, 259,714 rectal). A total of 113,322 patients developed secondary malignancies after RT (Table), with 26,299 developing secondary pelvic malignancies after RT (18,411 prostate, 1,026 bladder, 1,410 cervical, 2,179 uterine, 3,273 rectal) (Table). The overall relative risk (RR) of RT on developing a secondary malignancy was 1.79 (1.77-1.80 CI, P&lt;0.0001), particularly in patients with prostate (RR 2.57), uterine (RR 1.24) and cervical cancer (1.09). The overall RR of RT on developing a secondary pelvic malignancy was 2.09 (2.06-2.13 CI, P&lt;0.0001), particularly in patients with bladder (RR 6.90), prostate (RR 2.74), and uterine cancer (RR 1.21). Conclusions: Radiation treatment for pelvic malignancies increases the risk of developing secondary malignancies over the patient’s lifetime. Further work needs to done to identify at risk populations.[Table: see text]
Effect of PSMA-positive membranes secreted from prostate cancer cells on vascular endothelial cells.
Authors: Ryuta Watanabe, Masashi Maekawa, Takeshi Kiyoi, Mie Kurata, Noriyoshi Miura, Tadahiko Kikugawa, Shigeki Higashiyama, Takashi Saika
Journal: Journal of Clinical Oncology (2022)

141 Background: Prostate-specific membrane antigen (PSMA) is highly expressed in poorly differentiated, metastatic, and castration-resistant prostate cancers. Recently, 68Ga-PSMA positron emission tomography/computed tomography has been successfully developed as an effective diagnostic tool for prostate cancer. However, the pathophysiological functions of PSMA in prostate tumors remain unclear. Methods: We examined the protein expression of PSMA in tumor endothelial cells in human prostate tumors by immunohistochemistry. Prostate cancer tissues were resected from patients with prostate cancer via robotic surgery in 2019 at Ehime University. In vitro, we prepared conditioned medium derived from a PSMA-positive human prostate cancer cell line, LNCaP, cultured on collagen I gels. We then examined PSMA expression in human umbilical vascular endothelial cells (HUVECs) cultured with the conditioned medium. We assessed angiogenic activities by treating HUVECs with LNCaP-derived conditioned medium using a tube formation assay that mimics angiogenesis. Results: Immunohistochemical positivity of PSMA and CD31, a marker of endothelial cells, and PSMA-expressing tumor endothelial cells were observed in four of 33 prostate cancer patients (12.1%). We also found that the 10,000 ´ g pellet fraction of the LNCaP-derived conditioned medium containing PSMA-positive membranes, including microvesicles, transformed HUVECs from “PSMA-negative” to “PSMA-positive.” Mass spectrometry revealed that the fraction contained an important growth factor. Furthermore, treating HUVECs with the 10,000 ´ g pellet fraction of the LNCaP-derived conditioned medium significantly promoted tube formation, mimicking angiogenesis in a PSMA-dependent manner. Conclusions: Our findings revealed the existence of PSMA-positive tumor endothelial cells in human prostate tumors, which were found to enhance tumor angiogenesis in prostate cancer tissues. The endocytic process related to these PSMA-positive microvesicles in normal endothelial cells might be an attractive target to develop novel anti-angiogenic drugs, which could inhibit the transformation of normal endothelial cells into tumor endothelial cells (Watanabe et al., The Prostate. 2021. in press).
"B12 Shots"
Authors: Paul R. McCurdy
Journal: JAMA (1974)

An ironic "in joke" among hematologists goes something like this: "Look at the sales of vitamin B<sub>12</sub>! We must be missing a lot of PA." In truth, there isn't much pernicious anemia in the country, but there is a lot of B<sub>12</sub>in American deltoid and gluteus. VITAMIN B<sub>12</sub>is essential for cell multiplication and for normal function of the nervous system.<sup>1-3</sup>Symptoms of its deficiency may be vague and include fatigue, irritability, paresthesias, and problems with mentation. Although there may not be anemia, it is usually present, macrocytic, and sometimes severe. Subclinical nutritional deficiency is believed by many to be common and often nonspecifically symptomatic. In some cases, this may be true (eg, iron deficiency in the menstruating female). Consequently, it is not surprising that cyanocobalamin ("B<sub>12</sub>") shots are frequently administered to patients who are vaguely ill, worried but well, or merely desirous of
Depressive illness and aggression in Belfast.
Authors: H A Lyons
Journal: BMJ (1972)

idealistic perfection, our's of the practical care of children.Finally, a standard dosage regimen recom- mended for nitrofurantoin is 7 mg/kg/24 hours.'For a 2-year-old weighing approximately 12 kg 75 mg per day is not excessive.Not being blessed with foresight, we were not able to foresee the results firom Professor de Wardener's department that Dr. Bailey refers to,2 as these had not been published at the time we draf:ed our article, let alone at the time we were treating the child con- oerned.-Weare, etc.,
Waning efficacy of COVID-19 vaccination at six months in patients (pts) with genitourinary malignancies.
Authors: Zeynep Busra Zengin, Luis A Meza, Jasnoor Malhotra, Sabrina Salgia, Jennifer Ely, Joann Hsu, Erin Kelley, Heather Mead, Nazli Dizman, Alex Chehrazi-Raffle, Ameish Govindarajan, Ramya Muddasani, Neal Shiv Chawla, Tanya B. Dorff, Yung Lyou, Ewa Karczewska, Jeffrey M. Trent, Ravi Salgia, John Altin, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2022)

185 Background: Short-term effectiveness of COVID-19 vaccination is widely demonstrated, but the emerging real-world data suggest that immunity may wane over-time (Levin et al. NEJM 2021). Herein we aimed to explore the long-term efficacy of the COVID-19 vaccination among pts with genitourinary cancer. Methods: In this study, pts with genitourinary malignancies (prostate, kidney, and bladder cancers) who had not received COVID-19 vaccination were included. Blood samples were collected prior to and after one dose of either an adenovirus- or mRNA-based COVID-19 vaccine at the 2- and 6-month timepoints. Additional blood samples from pts receiving systemic treatment were collected at 3 consecutive therapy cycles following vaccination. Antibody titers were assessed using the SCoV-2 Detect IgG ELISA assay and results were reported as immune status ratios (ISR). T-cell receptor (TCR) repertoire sequencing was performed using the MiXCR software (MiLabs) and custom strips were used to assess TCR abundance and homology clustering. Results: A total of 183 pts were enrolled, and 136 pts provided baseline blood samples. Among these, 59 (8:51 F:M) provided samples for both the 2- and 6-month timepoints by the 10/6/2021 data cut-off. In this subset of pts, median age was 66 (range 48-85) and 33 (55.9%), 25 (42.4%), and 1 (1.7%) pts had prostate, kidney, and bladder cancer, respectively. A majority of the pts (93.2%) were on systemic treatment with 23.7% on immune checkpoint inhibitors, 18.6% on targeted agents, and 1.7% on chemotherapy. The most commonly administered vaccines were BNT162b2 (61.0%) followed by mRNA-1273 (37.3%) and Ad26.COV2.S (1.7%). The mean (±standard deviation) ISR values at baseline and 2 months were 0.68±1.59 and 6.62±1.75, respectively. At the 6-month timepoint, mean ISR was 5.46±1.61; this was significantly lower than the 2-month antibody titers (p &lt; 0.0001), and reflects a reduction of 17.6%. Further data on TCR sequencing will be presented at the meeting. Conclusions: To our knowledge, this is the first data assessing the long-term serologic outcomes of COVID-19 vaccination in pts with cancer. Our data suggest waning immunity over time in cancer pts. Strategies to prolong host immunity against SARS COV-2 (e.g., booster vaccination) are likely warranted.