tbuckley/cabot-search huggingface dataset:
Metabolic imaging detects elevated glucose flux through the pentose phosphate pathway associated with TERT expression in low-grade gliomas
Authors: Pavithra Viswanath, Georgios Batsios, Vinay Ayyappan, Céline Taglang, Anne Marie Gillespie, Peder E Z Larson, H Artee Luchman, Joseph F Costello, Russell O Pieper, Sabrina M Ronen
Journal: Neuro-Oncology (2021)

Abstract Background Telomerase reverse transcriptase (TERT) is essential for tumor proliferation, including in low-grade oligodendrogliomas (LGOGs). Since TERT is silenced in normal cells, it is also a therapeutic target. Therefore, noninvasive methods of imaging TERT are needed. Here, we examined the link between TERT expression and metabolism in LGOGs, with the goal of leveraging this information for noninvasive magnetic resonance spectroscopy (MRS)-based metabolic imaging of LGOGs. Methods Immortalized normal human astrocytes with doxycycline-inducible TERT silencing, patient-derived LGOG cells, orthotopic tumors, and LGOG patient biopsies were studied to determine the mechanistic link between TERT expression and glucose metabolism. The ability of hyperpolarized [U-13C, U-2H]-glucose to noninvasively assess TERT expression was tested in live cells and orthotopic tumors. Results TERT expression was associated with elevated glucose flux through the pentose phosphate pathway (PPP), elevated NADPH, which is a major product of the PPP, and elevated glutathione, which is maintained in a reduced state by NADPH. Importantly, hyperpolarized [U-13C, U-2H]-glucose metabolism via the PPP noninvasively reported on TERT expression and response to TERT inhibition in patient-derived LGOG cells and orthotopic tumors. Mechanistically, TERT acted via the sirtuin SIRT2 to upregulate the glucose transporter GLUT1 and the rate-limiting PPP enzyme glucose-6-phosphate dehydrogenase. Conclusions We have, for the first time, leveraged a mechanistic understanding of TERT-associated metabolic reprogramming for noninvasive imaging of LGOGs using hyperpolarized [U-13C, U-2H]-glucose. Our findings provide a novel way of imaging a hallmark of tumor immortality and have the potential to improve diagnosis and treatment response assessment for LGOG patients.
Advancing cancer research during challenging times
Authors: N. Sharpless
Journal: Cancer Research (2021)

The impact of the COVID-19 pandemic on care for people with cancer and the conduct of cancer research havebeen significant and will be evident for many years to come  While the National Cancer Institute (NCI) has broughtto bear considerable expertise and capabilities to respond to the pandemic, our top priority remains advancingcancer research  The NCI budget, activities in response to the pandemic, breast cancer research advances, and thevision for cancer clinical trials will be discussed
Abstract IA-011: Translation to clinical trials: Are we shooting the right arrows at the target?
Authors: Ricky A. Sharma
Journal: Clinical Cancer Research (2021)

Abstract Dependent on the stage of the cancer, 25-40% of patients require curative or palliative radiotherapy as part of their primary care treatment. The DNA Damage response (DDR) pathways have been a major area of interest for drug development as tumors often harbor mutations in the DDR pathways. The development of new DDR inhibitors offers wide-ranging opportunities to combine DDR inhibition with radiation therapy. Emerging evidence also supports the use of DDR inhibitors to promote immune stimulatory effects of radiation therapy by further activating the DNA sensing cGAS-STING pathway. DDR inhibitors in combination with RT have been shown to alter PDL-1 expression and have also been linked to modulating cytokine expression to alter the tumor microenvironment. This should be considered in the context of over 300 clinical trials ongoing which are combining immunotherapy with radiotherapy and important clinical studies of this combination therapy which have been published in patients with lung cancer. Significant progress is being made in understanding new drug-radiotherapy combinations and advancing them towards the clinic. Citation Format: Ricky A. Sharma. Translation to clinical trials: Are we shooting the right arrows at the target? [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-011.
Evaluation of the Safety of Calcitonin Gene-Related Peptide Antagonists for Migraine Treatment Among Adults With Raynaud Phenomenon
Authors: Ilana D. Breen, Caitlin M. Brumfiel, Meera H. Patel, Richard J. Butterfield, Juliana H. VanderPluym, Leroy Griffing, Mark R. Pittelkow, Aaron R. Mangold
Journal: JAMA Network Open (2021)

Calcitonin gene-related peptide (CGRP) antagonists have demonstrated tremendous promise in migraine management. However, these medications decrease reflex vasodilatory response, which may lead to exacerbation of microvascular disease in susceptible patients, such as patients with Raynaud phenomenon (RP).To investigate the microvascular complications of CGRP antagonists in patients with underlying RP.This retrospective cohort study was performed from May 18, 2018, to September 15, 2020, in Mayo Clinic Health System patients with Raynaud phenomenon while undergoing CGRP antagonist therapy to treat migraine. Inclusion criteria were age older than 18 years, history of migraine, past or current treatment with CGRP antagonists, and diagnosis of primary or secondary RP.Treatment with CGRP antagonists.The main outcome measure was microvascular complications (eg, worsening RP, digital ulcerations, and gangrenous necrosis) after initiation of treatment with a CGRP antagonist. Patient demographic and clinical characteristics were compared between those who experienced complications and those who did not.A total of 169 patients (163 [96.4%] female; 151 [89.3%] non-Hispanic White; mean [SD] age, 46 [13] years) were identified. Of the 169 patients, 9 (5.3%) exhibited microvascular complications, ranging from worsening RP to gangrene and autonecrosis that required distal digit amputation. Comparative analysis did not find statistically significant differences in demographic or clinical characteristics between the 2 cohorts. All 9 patients with complications were female (mean [SD] age, 40 [12] years). Five of the 9 patients (55.6%) had previously diagnosed RP; in 3 the RP was primary, and 2 it was secondary to scleroderma. The other 4 patients (44.4%) were newly diagnosed with RP. Eight of the 9 patients (88.9%) had chronic migraine; 4 had migraine with aura, and 5 had migraine without aura. The CGRP antagonist agents temporally associated with the microvascular complications included galcanezumab (in 3 patients), erenumab (in 5 patients), and fremanezumab (in 1 patient).The results of this study indicate that microvascular complications of CGRP antagonist use in patients with underlying RP are uncommon. The incidence of serious adverse events, although rare, warrant caution when considering the use of these agents in patients with RP.
インターフェロンγ誘導CXCケモカイン(IP10及びMIG)は川崎病の病因の一部で重要な役割を果たしている
Authors: Kamisago Mitsuhiro, Katsube Yasuhiro, Fukazawa Ryuji, Abe Masanori, Ogawa Shunichi
Journal: Circulation (2010)
Laminin-521 is a Novel Target of Autoantibodies Associated with Lung Hemorrhage in Anti-GBM Disease
Authors: Cong-rong Shen, Xiao-yu Jia, Wentian Luo, Florina Olaru, Zhao Cui, Ming-hui Zhao, Dorin-Bogdan Borza
Journal: Journal of the American Society of Nephrology (2021)

Antiglomerular basement membrane (anti-GBM) disease is characterized by GN and often pulmonary hemorrhage, mediated by autoantibodies that typically recognize cryptic epitopes within α345(IV) collagen-a major component of the glomerular and alveolar basement membranes. Laminin-521 is another major GBM component and a proven target of pathogenic antibodies mediating GN in animal models. Whether laminin-521 is a target of autoimmunity in human anti-GBM disease is not yet known.A retrospective study of circulating autoantibodies from 101 patients with anti-GBM/Goodpasture's disease and 85 controls used a solid-phase immunoassay to measure IgG binding to human recombinant laminin-521 with native-like structure and activity.Circulating IgG autoantibodies binding to laminin-521 were found in about one third of patients with anti-GBM antibody GN, but were not detected in healthy controls or in patients with other glomerular diseases. Autoreactivity toward laminin-521 was significantly more common in patients with anti-GBM GN and lung hemorrhage, compared with those with kidney-limited disease (51.5% versus 23.5%, P=0.005). Antilaminin-521 autoantibodies were predominantly of IgG1 and IgG4 subclasses and significantly associated with lung hemorrhage (P=0.005), hemoptysis (P=0.008), and smoking (P=0.01), although not with proteinuria or serum creatinine at diagnosis.Besides α345(IV) collagen, laminin-521 is another major autoantigen targeted in anti-GBM disease. Autoantibodies to laminin-521 may have the potential to promote lung injury in anti-GBM disease by increasing the total amount of IgG bound to the alveolar basement membranes.
Predictors of Chronic Opioid Use: A Population-Level Analysis of North Carolina Cancer Survivors Using Multi-Payer Claims
Authors: Devon K Check, Christopher D Baggett, KyungSu Kim, Andrew W Roberts, Megan C Roberts, Timothy Robinson, Kevin C Oeffinger, Michaela A Dinan
Journal: JNCI Journal of the National Cancer Institute (2021)

No population-based studies have examined chronic opioid use among cancer survivors who are diverse with respect to diagnosis, age group, and insurance status.We conducted a retrospective cohort study using North Carolina cancer registry data linked with claims from public and private insurance (2006-2016). We included adults with nonmetastatic cancer who had no prior chronic opioid use (n = 38 366). We used modified Poisson regression to assess the adjusted relative risk of chronic opioid use in survivorship (>90-day continuous supply of opioids in the 13-24 months following diagnosis) associated with patient characteristics.Only 3.0% of cancer survivors in our cohort used opioids chronically in survivorship. Predictors included younger age (adjusted risk ratio [aRR] 50-59 vs 60-69 = 1.23, 95% confidence interval [CI] = 1.05 to 1.43), baseline depression (aRR = 1.22, 95% CI = 1.06 to 1.41) or substance use (aRR = 1.43, 95% CI = 1.15 to 1.78) and Medicaid (aRR vs private = 1.93, 95% CI = 1.56 to 2.40). Survivors who used opioids intermittently (vs not at all) before diagnosis were twice as likely to use opioids chronically in survivorship (aRR = 2.62, 95% CI = 2.28 to 3.02). Those who used opioids chronically (vs intermittently or not at all) during active treatment had a nearly 17-fold increased likelihood of chronic use in survivorship (aRR = 16.65, 95% CI = 14.30 to 19.40).Younger and low-income survivors, those with baseline depression or substance use, and those who require chronic opioid therapy during treatment are at increased risk for chronic opioid use in survivorship. Our findings point to opportunities to improve assessment of psychosocial histories and to engage patients in shared decision-making around long-term pain management, when chronic opioid therapy is required during treatment.
Narrowing the Genomic Region of Autosomal-Dominant Congenital Generalized Hypertrichosis Terminalis
Authors: Ran Mo, Zhe Xu, Huijun Wang, Wei Yan, Xingyuan Jiang, Zhimiao Lin
Journal: JAMA Dermatology (2021)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Dermatology journal
Prescribing of Opioid Analgesics and Buprenorphine for Opioid Use Disorder During the COVID-19 Pandemic
Authors: Janet M. Currie, Molly K. Schnell, Hannes Schwandt, Jonathan Zhang
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The COVID-19 pandemic disrupted medical care, impacting prescribing of opioid analgesics and buprenorphine for opioid use disorder. Understanding these patterns can help address barriers to care. <h3>Objective</h3> To evaluate how prescribing of opioid analgesics and buprenorphine for opioid use disorder changed throughout the COVID-19 pandemic among both new and existing patients. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, use of opioid analgesics and buprenorphine for opioid use disorder from March 18 to September 1, 2020, was projected using a national database of retail prescriptions from January 1, 2018, to March 3, 2020. Actual prescribing was compared with projected levels for all, existing, and new patients. <h3>Exposures</h3> The data include prescriptions to patients independent of insurance status or type and cover 90% of retail prescriptions, 70% of mail-order prescriptions, and 70% of nursing home prescriptions. <h3>Main Outcomes and Measures</h3> Prescriptions for opioid analgesics and buprenorphine for opioid use disorder. Outcomes included total number of prescriptions, total morphine milligram equivalents, mean morphine milligram equivalents per prescription, mean dispensed units per prescription, and number of patients filling prescriptions. <h3>Results</h3> A total of 452 691 261 prescriptions for opioid analgesics and buprenorphine for opioid use disorder were analyzed for 90 420 353 patients (50 921 535 female patients [56%]; mean [SD] age, 49 [20] years). From March 18 to May 19, 2020, 1877 million total morphine milligram equivalents of opioid analgesics were prescribed weekly vs 1843 million projected, a ratio of 102% (95% prediction interval [PI], 94%-111%;<i>P</i> = .71). The weekly number of opioid-naive patients receiving opioids was 370 051 vs 564 929 projected, or 66% of projected (95% PI, 63%-68%;<i>P</i> &lt; .001). Prescribing of buprenorphine was as projected for existing patients, while the number of new patients receiving buprenorphine weekly was 9865 vs 12 008 projected, or 82% (95% PI, 76%-88%;<i>P</i> &lt; .001). From May 20 to September 1, 2020, opioid prescribing for new patients returned to 100% of projected (95% PI, 96%-104%;<i>P</i> = .95), while the number of new patients receiving buprenorphine weekly was 10 436 vs 11 613 projected, or 90% (95% PI, 83%-97%;<i>P</i> = .009). <h3>Conclusions and Relevance</h3> In this cross-sectional study, existing patients receiving opioid analgesics and buprenorphine for opioid use disorder generally maintained access to these medications during the COVID-19 pandemic. Opioid prescriptions for opioid-naive patients decreased briefly and then rebounded, while initiation of buprenorphine remained at a low rate through August 2020. Reductions in treatment entry may be associated with increased overdose deaths.
Re: Ming Yuen Teo, Jose Mauricio Mota, Karissa A. Whiting, et al. Fibroblast Growth Factor Receptor 3 Alteration Status is Associated with Differential Sensitivity to Platinum-based Chemotherapy in Locally Advanced and Metastatic Urothelial Carcinoma. Eur Urol 2020;78:907–15
Authors: Mathieu Roumiguie, Alberto Contreras-Sanz, Peter C. Black
Journal: European Urology (2021)
Glutathione S-Transferase P1 (GSTP1) is phosphorylated by Akt in human glioma cells
Authors: Tatsunori Okamura, Francis Ali-Osman
Journal: Cancer Research (2005)

4571  Akt (Protein kinase B, PKB), a serine/threonine kinase involved in cell growth and survival, contains a kinase domain which has structural similarity to those of PKC and PKA. Akt is up-regulated in a number of human cancers, notably glioblastoma multiforme, and plays crucial roles in the neoplastic biology of these tumors by phosphorylating critical downstream targets, such as, mTOR, GSK3 and the proapototic BAD proteins. We report here that the human glutathione S-transferase P1 (GSTP1) protein, a major drug/carcinogen metabolizing and stress response signaling protein, is a, heretofore unidentified, downstream target of Akt. In cell-free systems, we showed that the phosphorylation requires GSTP1 in its physiological, GSH-bound state. In MGR3 human glioblastoma cells, activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway was associated with significantly increased GSTP1 phosphorylation, which was also GSH-dependent. TLC mapping of the phosphorylated amino acids in Akt-phosphorylated GSTP1 showed the presence of both phosphorylated serine and threonine residues; the phosphorylation sites were subsequently confirmed by mass spectrometry. Preliminary data on the effects of the Akt phosphorylation on GSTP1 protein function will be presented. These findings, the first ever demonstration of GSTP1 as a downstream target of Akt, are significant in the context of malignant gliomas, in that the genetic background of these tumors, in particular, de novo GBM, includes mutations of the PTEN gene, that encodes a phosphatase whose action results in activation of the PI3K/Akt pathway. This, coupled with the overexpression and high activity of GSTP1 and the high levels of GSH in GBM cells, suggest that interaction of these two genetic characteristics could contribute to the drug resistance and aggressive biology of GBMs. Supported by grants RO1 CA91438, RO1 CA79644 and P20-CA096890 from the NIH (USA).
Breast lumps
Authors: M. Twoon, N. Y. B. Ng, S. E. Thomson
Journal: BMJ (2014)

A 35 year old woman presents with a 1 cm hard lump in the upper outer quadrant of her right breast. She first noticed this when she was in the shower three months ago. She is worried that the lump might be malignant. Breast lumps are common and have a variety of causes. Although most lumps are not malignant, any abnormal changes to the breasts need to be reviewed as soon as possible. Refer patients to a breast clinic where triple assessment can be performed and the lump fully investigated. It is often difficult to make a definitive diagnosis on clinical history and examination alone. Many patients who are referred for specialist assessment will be found not to have cancer. ### Examination Undertake a clinical breast examination, with consent and chaperone. People have different techniques and, although the following technique is recommended, it is by no means the only acceptable one.
Long Noncoding RNA PVT1 and MYC Are Co-Regulated By Bromodomain Protein BRD4 in Multiple Myeloma and Associated with Disease Progression
Authors: Kazuki Homma, Tsukasa Oda, Yuki Murakami, Saki Watanabe, Rei Ishihara, Yuko Kuroda, Kei Kimura Masuda, Yuta Masuda, Tetsuhiro Kasamatsu, Gotoh Nanami, Kenichi Tahara, Nobuhiko Kobayashi, Hiroaki Shimizu, Takuma Ishizaki, Akihiko Yokohama, Norifumi Tsukamoto, Takayuki Saitoh, Hirokazu Murakami, Hiroshi Handa
Journal: Blood (2017)
Dynamic compliance and reactance in older non-smokers with asthma and fixed airflow obstruction
Authors: Timothy Durack, David G. Chapman, Sandra Rutting, Cindy Thamrin, Gregory G. King, Katrina O. Tonga
Journal: European Respiratory Journal (2021)

<b>In older non-smokers with asthma and fixed airflow obstruction, <i>X</i><sub>5</sub> measured by oscillometry reflects dynamic rather than static compliance. Distinguishing between dynamic and static compliance is important as they are due to different factors.</b>https://bit.ly/3th0uEr
Simulating Outcomes of Cataract Surgery: Important Advances in Ophthalmology
Authors: Susana Marcos, Eduardo Martinez-Enriquez, Maria Vinas, Alberto de Castro, Carlos Dorronsoro, Seung Pil Bang, Geunyoung Yoon, Pablo Artal
Journal: Annual Review of Biomedical Engineering (2021)

As the human eye ages, the crystalline lens stiffens (presbyopia) and opacifies (cataract), requiring its replacement with an artificial lens [intraocular lens (IOL)]. Cataract surgery is the most frequently performed surgical procedure in the world. The increase in IOL designs has not been paralleled in practice by a sophistication in IOL selection methods, which rely on limited anatomical measurements of the eye and the surgeon's interpretation of the patient's needs and expectations. We propose that the future of IOL selection will be guided by 3D quantitative imaging of the crystalline lens to map lens opacities, anticipate IOL position, and develop fully customized eye models for ray-tracing-based IOL selection. Conversely, visual simulators (in which IOL designs are programmed in active elements) allow patients to experience prospective vision before surgery and to make more informed decisions about which IOL to choose. Quantitative imaging and optical and visual simulations of postsurgery outcomes will allow optimal treatments to be selected for a patient undergoing modern cataract surgery.
Inferring Adaptive Codon Preference to Understand Sources of Selection Shaping Codon Usage Bias
Authors: Janaina Lima de Oliveira, Atahualpa Castillo Morales, Laurence D Hurst, Araxi O Urrutia, Christopher R L Thompson, Jason B Wolf
Journal: Molecular Biology and Evolution (2021)

Alternative synonymous codons are often used at unequal frequencies. Classically, studies of such codon usage bias (CUB) attempted to separate the impact of neutral from selective forces by assuming that deviations from a predicted neutral equilibrium capture selection. However, GC-biased gene conversion (gBGC) can also cause deviation from a neutral null. Alternatively, selection has been inferred from CUB in highly expressed genes, but the accuracy of this approach has not been extensively tested, and gBGC can interfere with such extrapolations (e.g., if expression and gene conversion rates covary). It is therefore critical to examine deviations from a mutational null in a species with no gBGC. To achieve this goal, we implement such an analysis in the highly AT rich genome of Dictyostelium discoideum, where we find no evidence of gBGC. We infer neutral CUB under mutational equilibrium to quantify "adaptive codon preference," a nontautologous genome wide quantitative measure of the relative selection strength driving CUB. We observe signatures of purifying selection consistent with selection favoring adaptive codon preference. Preferred codons are not GC rich, underscoring the independence from gBGC. Expression-associated "preference" largely matches adaptive codon preference but does not wholly capture the influence of selection shaping patterns across all genes, suggesting selective constraints associated specifically with high expression. We observe patterns consistent with effects on mRNA translation and stability shaping adaptive codon preference. Thus, our approach to quantifying adaptive codon preference provides a framework for inferring the sources of selection that shape CUB across different contexts within the genome.
Corrigendum to ‘VP1-2021: Efficacy of everolimus in patients with HR+/HER2- high risk early stage breast cancer’
Authors: T. Bachelot, F. Dalenc, S. Chabaud, P. Cottu, D. Allouache, E. Brain, J.-P. Jacquin, J. Grenier, L. Venat Bouvet, M. Brunt, M. Campone, F. Del Piano, M. Debled, A.-C. Hardy Bessard, S. Giacchetti, J. Bliss, J.-L. Canon, J. Lemonnier, D. Cameron, F. André
Journal: Annals of Oncology (2021)