tbuckley/cabot-search huggingface dataset:
Activation of multiple molecular mechanisms for mediation of apoptosis in human malignant glioblastoma cell lines T98G and U87MG following exposure to L-sulforaphane
Authors: Surajit Karmakar, Marc S. Weinberg, Arabinda Das, Thomas Walle, Sunil J. Patel, Naren L. Banik, Swapan K. Ray
Journal: Cancer Research (2005)

816  Glioblastoma is the most malignant and prevalent brain tumor in humans. Various treatment strategies such as surgery, radiation therapy, chemotherapy, and/or an experimental therapy are being employed, still glioblastoma is not a curable cancer. Therefore, the search continues for an effective therapeutic strategy. Some recent studies suggest growth inhibitory effect of broccoli derived compound L-sulforaphane (L-SFN) on several cancers. In our investigation, we examined the capability of L-SFN for induction of apoptosis in human malignant glioblastoma cell lines T98G and U87MG, and also explored the activation of proteolytic mechanisms for mediation of apoptosis. Trypan blue dye exclusion test showed decreased viability of glioblastoma cells with increasing dose of L-SFN. Examination of Wright stained cells under the light microscopy identified apoptotic morphology following exposure to 20 μM and 40 μM L-SFN for 24 h. ApopTag assay detected DNA fragmentation in apoptotic cells. Fura-2 assay demonstrated an increase in intracellular free Ca2+, suggesting activation of Ca2+-dependent proteolytic pathways in apoptotic process. Western blot analyses indeed detected overexpression of 80 kD calpain, a Ca2+-dependent cysteine protease, and generation of active 76 kD calpain in apoptotic cells. Western blot analyses also suggested that activation of calpain could cleave 55 kD caspase-12 to generate active 40 kD caspase-12, which in turn could promote activation of caspase-3. Changes in expression of Bax and Bcl-2 proteins resulted in an increase in Bax:Bcl-2 ratio, showing a commitment of cells to apoptosis after exposure to L-SFN. As a consequence of increased Bax:Bcl-2 ratio, cytochrome c was released from mitochondria to cytosol to contribute to the activation of caspase-9 that in turn activated caspase-3. In course of apoptosis, increased expression of Smac/Diablo suggested suppression of inhibitor-of-apoptosis proteins (IAPs), which otherwise could prevent activation of caspases. Morevover, decreased expression of p65 NFκB and increased expression of IκBα favored the process of apoptosis. Activation of calpain and caspase-3 cleaved 270 kD α-spectrin at specific sites generating, respectively, 145 kD spectrin breakdown product (SBDP) and 120 kD SBDP. Further, activation of caspase-3 was confirmed in the fragmentation of inhibitor-of-caspase-3-activated-DNase (ICAD). Besides, over accumulation of apoptosis-inducing-factor (AIF) suggested an involvement of caspase-independent pathway of apoptosis as well. Taken together, all these results indicated activation of multiple molecular mechanisms for mediation of apoptosis in glioblastoma cells following exposure to L-SFN. This investigation was supported in part by the R01 grants from the NCI and NINDS of the NIH (Bethesda, MD), and also a grant from the State of SC.
Triglyceride lowering by omega-3 fatty acids: a mechanism mediated by N-acyl taurines
Authors: Karin E. Bornfeldt
Journal: Journal of Clinical Investigation (2021)

Interest in omega-3 fatty acids (colloquially known as fish oils) to lower residual cardiovascular risk in statin-treated patients has increased markedly in the wake of recent cardiovascular outcome trials. The triglyceride-lowering effects of omega-3 fatty acids are generally thought to occur by reduced hepatic VLDL production. In this issue of the JCI, Grevengoed et al. used mouse models and human plasma samples to reveal an additional mechanism whereby these polyunsaturated fatty acids can lower plasma triglycerides. Their findings indicate that omega-3 fatty acid–derived N-acyl taurines (NATs) greatly accumulate in bile and also in plasma following omega-3 supplementation. The authors further show that one of these NATs (C22:6 NAT) inhibited intestinal triglyceride hydrolysis and lipid absorption, which resulted in lower plasma triglycerides and protection against hepatic triacylglycerol accumulation in mice fed a high-fat diet. The findings open a potential avenue for triglyceride lowering by omega-3 fatty acids conjugated to taurine.
Brain ethanol metabolism by astrocytic ALDH2 drives the behavioural effects of ethanol intoxication
Authors: Shiyun Jin, Qi Cao, Fanghan Yang, Hongying Zhu, Su Xu, Qi Chen, Ziyi Wang, Yuhong Lin, Resat Cinar, Robert J. Pawlosky, Ye Zhang, Wei Xiong, Bin Gao, George F. Koob, David M. Lovinger, Li Zhang
Journal: Nature Metabolism (2021)
P83.01 Updated Survival and Biomarker Analysis of Camrelizumab and Apatinib in Previously Treated pts of Advanced Non-Squamous NSCLC
Authors: S. Ren, Y. Wang, J. Zhao, G. Chen, Z. Liu, K. Gu, M. Huang, J. He, J. Chen, Z. Ma, J. Feng, J. Shi, X. Yu, Y. Cheng, Y. Yao, Y. Chen, R. Guo, X. Lin, Z. Wang, G. Gao, Q. Wang, W. Li, X. Yang, C. Zhou
Journal: Journal of Thoracic Oncology (2021)
ALDH1a2 is a candidate tumor suppressor gene in prostate cancer
Authors: Hanna Y. Kim, Jacques Lapointe, James D. Brooks, Jonathan R. Pollack
Journal: Cancer Research (2005)

1835  Prostate cancer is the most common cancer among men in the United States, and aberrant DNA methylation is known to be an early molecular event in its development. Here, we have used expression profiling to identify novel hypermethylated genes whose expression is induced by treatment of prostate cancer cell lines with the DNA methyltransferase inhibitor 5-aza-dC. Of the 356 genes that were induced by 5-Aza-dC treatment, 49 also displayed reduced expression in primary prostate tumors compared to normal prostate tissue, and the decreased expression of only one gene, ALDH1a2 (Aldehyde dehydrogenase 1 family, member A2), was associated with reduced tumor-free survival. ALDH1a2 encodes an enzyme responsible for synthesis of retinoic acid, a compound with pro-differentiation properties. By immunohistochemistry, we observed that ALDH1a2 was expressed in epithelia from normal prostate but not prostate cancer. Using bisulfite sequencing, we determined that the ALDH1a2 promotor region was significantly hypermethylated in prostate cancer compared to normal prostate specimens (P=0.024). Finally, transfection-mediated re-expression of ALDH1a2 in the prostate cancer cell line DU145 resulted in decreased colony growth (P
P79.08 Sintilimab ± IBI305 Plus Chemotherapy for Patients With EGFR-Mutant Non-Squamous NSCLC Failed to EGFR-TKI Treatment
Authors: S. Lu, Y. Cheng, L. Wu, J. Fang, B. Li, L. Han, Y. Zhang, H. Pan, Z. Wang, Y. Sun, F. Ye, Y. Hu, W. Yu, H. Zhou
Journal: Journal of Thoracic Oncology (2021)
Historical Contingency Causes Divergence in Adaptive Expression of the <i>lac</i> Operon
Authors: Kedar Karkare, Huei-Yi Lai, Ricardo B.R. Azevedo, Tim F. Cooper
Journal: Molecular Biology and Evolution (2021)

Populations of Escherichia coli selected in constant and fluctuating environments containing lactose often adapt by substituting mutations in the lacI repressor that cause constitutive expression of the lac operon. These mutations occur at a high rate and provide a significant benefit. Despite this, eight of 24 populations evolved for 8,000 generations in environments containing lactose contained no detectable repressor mutations. We report here on the basis of this observation. We find that, given relevant mutation rates, repressor mutations are expected to have fixed in all evolved populations if they had maintained the same fitness effect they confer when introduced to the ancestor. In fact, reconstruction experiments demonstrate that repressor mutations have become neutral or deleterious in those populations in which they were not detectable. Populations not fixing repressor mutations nevertheless reached the same fitness as those that did fix them, indicating that they followed an alternative evolutionary path that made redundant the potential benefit of the repressor mutation, but involved unique mutations of equivalent benefit. We identify a mutation occurring in the promoter region of the uspB gene as a candidate for influencing the selective choice between these paths. Our results detail an example of historical contingency leading to divergent evolutionary outcomes.
Abstract 16564: Location of Persistent Atrial Fibrillation Drivers Based on Body Surface Mapping: A Systematic Review and Metanalysis
Authors: Abdullah Sarkar, Mauricio Tellez, Shane Saifman, Daniel Weitz
Journal: Circulation (2020)

Introduction: Body Surface Mapping (BSM) is a non-invasive electrocardiogram-based mapping system that is used to identify localized drivers in patients with persistent Atrial Fibrillation (AF). Mapping of local drivers is becoming increasingly important in guiding treatment of atrial fibrillation but may not be readily available. We conducted a systematic review to determine the most prevalent atrial regions of AF driver activity identified with BSM. Methods: Electronic literature searches were performed across PubMed, Google Scholar, Cochrane, CINAHL, Web of science, EMBASE databases up to January 2019, for studies that utilized BSM to identify and report localized focal and rotor (reentrant) driver activity. Prevalence of drivers, as a percentage, were recorded for every region according to the Bordeaux Biatrial Schema. Random-effects model was used to calculate weighted averages with the corresponding 95% confidence interval (CI). Results: Total of 468 unique studies were identified and reviewed. 4 prospective cohort studies were included in the final analysis—of which 3 were single-center and 1 was multi-centered; totaling 336 patients. The mean age was 62.8 (±5.41) and 73% were males. The three most prevalent regions with persistent AF foci activity were region 1 (left pulmonary veins and left appendage): 59% (CI 48-71), followed by region 4 (upper half of right atrium and appendage): 31% (CI 12-54), and region 2 (right pulmonary veins and posterior interatrial groove): 19% (CI 7-34). The three most prevalent regions of persistent AF rotor activity were region 3 (inferior and posterior left atrium): 71% (CI 32-98), region 1: 70% (CI 21-100), and region 2: 70% (CI 25-99). Conclusion: In patients with persistent AF, majority of localized drivers seem to originate from specific atrial regions based on BSM.
Early plasma circulating tumor DNA (ctDNA) changes predict response to first-line pembrolizumab-based therapy in non-small cell lung cancer (NSCLC)
Authors: Biagio Ricciuti, Greg Jones, Mariano Severgnini, Joao V Alessi, Gonzalo Recondo, Marissa Lawrence, Tim Forshew, Christine Lydon, Mizuki Nishino, Michael Cheng, Mark Awad
Journal: Journal for ImmunoTherapy of Cancer (2021)

Type 2 immunity plays an important role in host defense against helminths and toxins while driving allergic diseases. Despite progress in understanding the biology of type 2 immunity, the fundamental mechanisms regulating the type 2 immune module remain unclear. In contrast with structural recognition used by pattern recognition receptors, type 2 immunogens are sensed through their functional properties. Functional recognition theory has arisen as the paradigm for the initiation of type 2 immunity. However, the vast array of structurally unrelated type 2 immunogens makes it challenging to advance our understanding of type 2 immunity. In this article, we review functional recognition theory and organize type 2 immunogens into distinct classes based on how they fit into the concept of functional recognition. Lastly, we discuss areas of uncertainty in functional recognition theory with the goal of providing a framework to further define the logic of type 2 immunity in host protection and immunopathology.
Evaluation of State Cannabis Laws and Rates of Self-harm and Assault
Authors: Ellicott C. Matthay, Mathew V. Kiang, Holly Elser, Laura Schmidt, Keith Humphreys
Journal: JAMA Network Open (2021)

<h3>Importance</h3> State cannabis laws are changing rapidly. Research is inconclusive about their association with rates of self-harm and assault. Existing studies have not considered variations in cannabis commercialization across states over time. <h3>Objective</h3> To evaluate the association of state medical and recreational cannabis laws with self-harm and assault, overall and by age and sex, while considering varying degrees of commercialization. <h3>Design, Setting, and Participants</h3> Using a cohort design with panel fixed-effects analysis, within-state changes in claims for self-harm and assault injuries before and after changes in cannabis laws were quantified in all 50 US states and the District of Columbia. Comprehensive claims data on commercial and Medicare Advantage health plan beneficiaries from January 1, 2003, to December 31, 2017, grouped by state and month, were evaluated. Data analysis was conducted from January 31, 2020, to January 21, 2021. <h3>Exposures</h3> Categorical variable that indexed the degree of cannabis legalization in each state and month based on law type (medical or recreational) and operational status of dispensaries (commercialization). <h3>Main Outcomes and Measures</h3> Claims for self-harm and assault injuries based on<i>International Classification of Diseases</i>codes. <h3>Results</h3> The analysis included 75 395 344 beneficiaries (mean [SD] age, 47 [22] years; 50% female; and median follow-up, 17 months [interquartile range, 8-36 months]). During the study period, 29 states permitted use of medical cannabis and 11 permitted recreational cannabis. Point estimates for populationwide rates of self-harm and assault injuries were higher in states legalizing recreational cannabis compared with states with no cannabis laws, but these results were not statistically significant (adjusted rate ratio [aRR] assault, recreational dispensaries: 1.27; 95% CI, 0.79-2.03;self-harm, recreational dispensaries aRR: 1.15; 95% CI, 0.89-1.50). Results varied by age and sex with no associations found except for states with recreational policies and self-harm among males younger than 40 years (aRR &lt;21 years, recreational without dispensaries: 1.70; 95% CI, 1.11-2.61; aRR aged 21-39 years, recreational dispensaries: 1.46; 95% CI, 1.01-2.12). Medical cannabis was generally not associated with self-harm or assault injuries populationwide or among age and sex subgroups. <h3>Conclusions and Relevance</h3> Recreational cannabis legalization appears to be associated with relative increases in rates of claims for self-harm among male health plan beneficiaries younger than 40 years. There was no association between cannabis legalization and self-harm or assault, for any other age and sex group or for medical cannabis. States that legalize but still constrain commercialization may be better positioned to protect younger male populations from unintended harms.
Hypomagnesemia at the time of autologous stem cell transplantation for patients with diffuse large B-cell lymphoma is associated with an increased risk of failure
Authors: Jennifer J. Gile, Camden L. Lopez, Gordon J. Ruan, Matthew A. Hathcock, Jithma P. Abeykoon, Joy R. Heimgartner, Nikola A. Baumann, M. Molly McMahon, Ivana N. Micallef, Patrick B. Johnston, Jose C. Villasboas Bisneto, Luis F. Porrata, Jonas Paludo, Stephen M. Ansell, William J. Hogan, Thomas E. Witzig
Journal: Blood Cancer Journal (2021)

Abstract Magnesium is an essential element that is involved in critical metabolic pathways. A diet deficient in magnesium is associated with an increased risk of developing cancer. Few studies have reported whether a serum magnesium level below the reference range (RR) is associated with prognosis in patients with diffuse large B cell lymphoma (DLBCL). Using a retrospective approach in DLBCL patients undergoing autologous stem cell transplant (AHSCT), we evaluated the association of hypomagnesemia with survival. Totally, 581 patients eligible for AHSCT with a serum magnesium level during the immediate pre-transplant period were identified and 14.1% (82/581) had hypomagnesemia. Hypomagnesemia was associated with an inferior event-free (EFS) and overall survival (OS) compared to patients with a serum magnesium level within RR; median EFS: 3.9 years (95% CI: 1.63–8.98 years) versus 6.29 years (95% CI: 4.73–8.95 years) with HR 1.63 (95% CI: 1.09–2.43, p = 0.017) for EFS, and median OS: 7.3 years (95% CI: 2.91—upper limit not estimable) versus 9.7 years (95% CI: 6.92–12.3 years) with HR 1.90 (95% CI: 1.22–2.96, p = 0.005) for OS months 0–12, respectively. These findings suggest a potentially actionable prognostic factor for patients with DLBCL undergoing AHSCT.
Neonatal Lupus Erythematosus
Authors: Jianni Wu, Juliana Berk-Krauss, Sharon A. Glick
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
Progressive Papular Eruption of the Distal Upper Extremities in a Patient With Asymptomatic Papules
Authors: Misty M. Hobbs, Matthew Hall, Jason C. Sluzevich
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
Reducing Immunogenicity of Pegloticase With Concomitant Use of Mycophenolate Mofetil in Patients With Refractory Gout: A Phase II, Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Puja P. Khanna, Dinesh Khanna, Gary Cutter, Jeff Foster, Joshua Melnick, Sara Jaafar, Stephanie Biggers, A. K. M. Fazlur Rahman, Hui‐Chien Kuo, Michelle Feese, Alan Kivitz, Charles King, William Shergy, Jeff Kent, Paul M. Peloso, Maria I. Danila, Kenneth G. Saag
Journal: Arthritis & Rheumatology (2021)

Pegloticase is used for the treatment of severe gout, but its use is limited by immunogenicity. This study was undertaken to evaluate whether mycophenolate mofetil (MMF) prolongs the efficacy of pegloticase.Participants were randomized 3:1 to receive 1,000 mg MMF twice daily or placebo for 14 weeks, starting 2 weeks before receiving pegloticase and continuing while receiving intravenous pegloticase 8 mg biweekly for 12 weeks. Participants then received pegloticase alone from week 12 to week 24. The primary end points were the proportion of patients who sustained a serum urate level of ≤6 mg/dl at 12 weeks and the rate of adverse events (AEs). Secondary end points included 24-week durability of serum urate level ≤6 mg/dl. Fisher's exact test and Wilcoxon's 2-sample test were used for analyses, along with Kaplan-Meier estimates and log rank tests.A total of 32 participants received ≥1 dose of pegloticase. Participants were predominantly men (88%), with a mean age of 55.2 years, mean gout duration of 13.4 years, and mean baseline serum urate level of 9.2 mg/dl. At 12 weeks, a serum urate level of ≤6 mg/dl was achieved in 19 (86%) of 22 participants in the MMF arm compared to 4 (40%) of 10 in the placebo arm (P = 0.01). At week 24, the serum urate level was ≤6 mg/dl in 68% of MMF-treated patients versus 30% of placebo-treated patients (P = 0.06), and rates of AEs were similar between groups, with more infusion reactions occurring in the placebo arm (30% versus 0%).Our findings indicate that MMF therapy with pegloticase is well tolerated and shows a clinically meaningful improvement in targeted serum urate level of ≤6 mg/dl at 12 and 24 weeks. This study suggests an innovative approach to pegloticase therapy in gout.
Long-term Performance of Epic and PERIMOUNT Mitral Bioprostheses in Young Rheumatics
Authors: Ujjwal Chowdhury
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Objective: We compared the long-term cossmposites of valve-related reoperation, morbidity and mortality following two types of mitral bioprostheses in young rheumatics aged &lt;45 years. Methods: Retrospective comparative analysis of structural valve-related reoperations, and survival data were performed on 260 propensity matched patients, undergoing bioprosthetic MVR between 2000 and 2019, using Epic (Group I, n=130) or PERIMOUNT bioprostheses (Group II, n=130). Results: The median age was 34.5 (IQR: 28-39) and 34 (IQR: 29-40) years for group I and II respectively. Hazard regression for mortality included HR (95% CI) preoperative congestive heart failure (CHF) 4.70 (1.76-12.56), p=0.002; renal failure 66.91 (12.88-347.59), p&lt;0.0001; low left ventricular ejection fraction &lt;0.25, 3.76 (1.72-7.27), p=0.004; and valve-related reoperations 3.82 (1.81-9.56), p=0.001. Although the structural valve degeneration (SVD)-related reoperations were more among the perimount group, propensity score matching did not exhibit any difference between the groups [8.5% (Group I) vs 14.6% (Group II), SMD -0.23, p=0.5]. At a median follow-up of 134 (IQR: 99.5-178.5) months, actuarial survival was 96.36%±0.01% (93.11-98.10), and there was no difference in survival between the groups (Log rank p=0.70). Conclusions: Both Epic and PERIMOUNT mitral bioprostheses provide similar long-term clinical outcomes and are an appealing alternative to mechanical prosthesis in younger rheumatics.
A Compendium of Transcriptional and Mutational Data to Improve the Stratification of Peripheral T-Cell Lymphoma Subtypes
Authors: Francesco Maura, Luca Agnelli, Tayla Heavican, Anna Dodero, Cristiana Carniti, John Chan, Yu Jiayu, Alessio Pellegrinelli, Antonello Domenico Cabras, Niccolò Bolli, Annalisa Chiappella, Daniel Leongamornlert, Alice Di Rocco, Michela Ansuinelli, Francesco Zaja, Umberto Vitolo, Roberto Piva, Wenyi Wang, Antonino Neri, Javeed Iqbal, Paolo Corradini
Journal: Blood (2017)
P76.85 Afatinib and Necitumumab in EGFR mutant NSCLC with Acquired Resistance to 1st or 3rd Generation EGFR Tyrosine Kinase Inhibitors
Authors: S. Padda, J. Whisenant, J. Neal, S. York, W. Iams, M. Neuss, K. Reckamp, J. Preiss, L. Berry, Y. Shyr, H. Wakelee, L. Horn
Journal: Journal of Thoracic Oncology (2021)
T4/M1LYM食道癌患者(pts)における限定的な化学放射線療法(CRT)の長期毒性と残存
Authors: Minashi K, Ohtsu A, Mera K, Yoshida S, Ishikura S, Ogino T, Boku N, Miyata Y, Kaneko K, Nakamura A
Journal: Journal of Clinical Oncology (2004)