tbuckley/cabot-search huggingface dataset:
Deciphering Treg accumulation in melanoma.
Authors: Kristen E. Tobin Vealey, I. Caroline Le Poole, Jared S. Klarquist, Jonathan M. Eby
Journal: Journal of Clinical Oncology (2013)

e22170 Background: A high density of regulatory T-cells (Tregs) at melanoma tumor sites correlates with poor prognosis due to immunosuppressive effects on the host immune system. While the concentration of circulating Tregs in patients with melanoma is not significantly different from that of healthy controls, Tregs tend to accumulate at tumor sites. We hypothesized that the influx of Tregs observed in melanoma tumors may be explained by enhanced tumor homing. Methods: To quantify the relative expression of chemokine receptors CCL4 and CCL8, and skin homing receptor CLA, blood was drawn from five metastatic melanoma patients and five healthy controls. Lymphocytes were ficolled and negatively sorted for CD3 expression. T-cells were subjected to 7-color FACS staining where Tregs were defined as CD4 + CD25 + CD127 low FoxP3 + and were simultaneously assessed for expression of CCR4, CCR8, and CLA. To further understand chemokine-receptor signaling involved in Treg homing in melanoma we analyzed the number of CCL22 producing cells in four human metastatic melanoma tissues and four healthy skin tissues obtained during surgery. Dermal CCL22 + cells were detected by indirect immunohistochemistry and quantified to a depth of three times the thickness of the epidermis. Results: Lymphocytes of melanoma patients were found to exhibit enhanced expression of CCR4 (mean of 65.9 versus 51.2%, p&lt;0.01) and CCR8 (3.0 versus 1.5%, p&lt;0.05), but not CLA (21.9 versus 23.9%) as compared with healthy controls. The mean fluorescence intensities of CCR4 and CCR8 were likewise elevated by 63 and 49% over controls (p&lt;0.05 and p&lt;0.01), respectively. A markedly increased number of CCL22 secreting cells were found in tumor samples (mean of 1063.1 versus 207.4, p= 0.02) as compared with healthy controls. Conclusions: These data strongly suggest that enhanced homing of CCR4+ Tregs towards the ligand CCL22 is likely involved in accumulating Tregs at melanoma tumor sites, ultimately impeding effective anti-tumor immune responses. Targeting chemokine-receptor signaling may thus be an effective intervention strategy in melanoma.
A State-of-the-Science Review of Arsenic’s Effects on Glucose Homeostasis in Experimental Models
Authors: Felicia Castriota, Linda Rieswijk, Sarah Dahlberg, Michele A. La Merrill, Craig Steinmaus, Martyn T. Smith, Jen-Chywan Wang
Journal: Environmental Health Perspectives (2020)

Background: The prevalence of type 2 diabetes (T2D) has more than doubled since 1980. Poor nutrition, sedentary lifestyle, and obesity are among the primary risk factors. While an estimated 70% of cases are attributed to excess adiposity, there is an increased interest in understanding the contribution of environmental agents to diabetes causation and severity. Arsenic is one of these environmental chemicals, with multiple epidemiology studies supporting its association with T2D. Despite extensive research, the molecular mechanism by which arsenic exerts its diabetogenic effects remains unclear. Objectives: We conducted a literature search focused on arsenite exposure in&nbsp;vivo and in vitro, using relevant end points to elucidate potential mechanisms of oral arsenic exposure and diabetes development. Methods: We explored experimental results for potential mechanisms and elucidated the distinct effects that occur at high vs. low exposure. We also performed network analyses relying on publicly available data, which supported our key findings. Results: While several mechanisms may be involved, our findings support that arsenite has effects on whole-body glucose homeostasis, insulin-stimulated glucose uptake, glucose-stimulated insulin secretion, hepatic glucose metabolism, and both adipose and pancreatic β-cell dysfunction. Discussion: This review applies state-of-the-science approaches to identify the current knowledge gaps in our understanding of arsenite on diabetes development. https://doi.org/10.1289/EHP4517
Induction of Truncating ASXL1 Mutations in Human CD34+ HSPCs Mimics Human ASXL1-Mutated Clonal Hematopoiesis and Progression to Myeloid Malignancies
Authors: Thomas Koehnke, Rajiv Sharma, Yusuke Nakauchi, Andreas Reinisch, Ravi Majeti
Journal: Blood (2019)
Transient Switch to Myeloid Lineage in Acute Lymphoblastic Leukemia during Induction Therapy: The Role of CD371 Expression and Implication for Minimal Residual Disease Detection
Authors: Elena Varotto, Margarita Maurer-Granofszky, Daniela Silvestri, Pamela Scarparo, Ester Mejstrikova, Monika Brüggemann, Giovanni Cazzaniga, Valentino Conter, Ondrej Hrusak, Giuseppe Gaipa, Angela Schumich, Maria Grazia Valsecchi, Giuseppe Basso, Michael Dworzak, Barbara Buldini
Journal: Blood (2019)
Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species
Authors: Serena Manara, Francesco Asnicar, Francesco Beghini, Davide Bazzani, Fabio Cumbo, Moreno Zolfo, Eleonora Nigro, Nicolai Karcher, Paolo Manghi, Marisa Isabell Metzger, Edoardo Pasolli, Nicola Segata
Journal: Genome biology (2019)

Humans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative metagenomic analysis of human and non-human primate (NHP) microbiomes offers a promising approach to study this symbiosis. Very few microbial species have been characterized in NHP microbiomes due to their poor representation in the available cataloged microbial diversity, thus limiting the potential of such comparative approaches.We reconstruct over 1000 previously uncharacterized microbial species from 6 available NHP metagenomic cohorts, resulting in an increase of the mappable fraction of metagenomic reads by 600%. These novel species highlight that almost 90% of the microbial diversity associated with NHPs has been overlooked. Comparative analysis of this new catalog of taxa with the collection of over 150,000 genomes from human metagenomes points at a limited species-level overlap, with only 20% of microbial candidate species in NHPs also found in the human microbiome. This overlap occurs mainly between NHPs and non-Westernized human populations and NHPs living in captivity, suggesting that host lifestyle plays a role comparable to host speciation in shaping the primate intestinal microbiome. Several NHP-specific species are phylogenetically related to human-associated microbes, such as Elusimicrobia and Treponema, and could be the consequence of host-dependent evolutionary trajectories.The newly reconstructed species greatly expand the microbial diversity associated with NHPs, thus enabling better interrogation of the primate microbiome and empowering in-depth human and non-human comparative and co-diversification studies.
Response to Open Peer Commentaries “Taxonomizing Views of Clinical Ethics Expertise”
Authors: Abram Brummett, Erica Salter
Journal: The American Journal of Bioethics (2020)

Address correspondence to Abram Brummett, Alden March Bioethics Institute, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA. E-mail: Brummea@amc.edu
Vitamin D Receptor (VDR) gene polymorphisms, calcium intake, and breast cancer risk among U.S. women
Authors: Marjorie L. McCullough, Victoria L. Stevens, W. Ryan Diver, Carmen Rodriguez, Heather S. Feigelson, Michael J. Thun, Eugenia E. Calle
Journal: Cancer Research (2005)

5813  Background: Circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) has potent effects on cell growth and differentiation via binding with the nuclear vitamin D receptor (VDR). Three SNPs in the VDR gene (BsmI, TaqI and ApaI) are in strong linkage disequilibrium and have previously been associated with breast cancer risk in some studies, possibly through linkage with a variable length poly (A) in the 3’ untranslated region. High dietary calcium intake may modify associations between VDR genotype and breast cancer risk by down-regulating circulating 1,25(OH)2D levels. Methods: We conducted a nested case control study of the association of BsmI, ApaI and TaqI VDR genotypes, and their associated haplotypes with postmenopausal breast cancer risk among women in the American Cancer Society’s Cancer Prevention Study II Nutrition Cohort. Participants completed a 10-page questionnaire in 1992 on diet, medical history and breast cancer risk factors. Among 21,965 women who gave blood in 1998-2001 and were cancer free at baseline in 1992, 498 breast cancer cases were diagnosed between 1992-2001; 502 controls were matched on age, race/ethnicity, and date of blood collection. DNA was extracted from buffy coat and genotyping assays were performed using Taqman (Applied Biosystems, Foster City, CA). Unconditional logistic regression was used to examine the association between each polymorphism and breast cancer risk while controlling for matching factors and other possible risk factors. Results: Associations were similar among those with one or two variant alleles or haplotype copies; consequently we present them combined. Breast cancer risk was not statistically different in individuals with a variant allele for BsmI (BB/Bb vs bb): OR=1.21, 95% CI 0.91-1.62 or TaqI (tt/tT vs TT): OR=1.19, 95% CI 0.90-1.57, or the ApaI homozygous wildtype (AA vs Aa/aa): OR=1.20, 95% CI 0.89-1.61. Having at least one copy (compared to no copies) of the BAt haplotype yielded similar results (OR=1.21, 95% CI 0.92-1.60). However, among women with greater than median intake of total calcium (diet plus supplements, ≥902 mg/day vs.
Association of Physician Peer Influence With Subsequent Physician Adoption and Use of Bevacizumab
Authors: Nancy L. Keating, A. James O’Malley, Jukka-Pekka Onnela, Stacy W. Gray, Bruce E. Landon
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Understanding adoption of new cancer therapies may help identify opportunities to increase use for high-value indications. <h3>Objective</h3> To determine whether use of bevacizumab in 2005 to 2006 by oncologists' peers was associated with greater bevacizumab use among oncologists in 2007 to 2010. <h3>Design, Setting, and Participants</h3> This cohort study of physicians and their patients took place in 51 randomly selected hospital referral regions in the United States. Participants were 44 012 fee-for-service Medicare beneficiaries aged 65 years or older with cancers of the colorectum, lung, breast, kidney, brain, or ovary treated by 3261 oncologists in 2005 to 2010 and assigned to one of 252 communities. Data were analyzed in 2017 to 2018. <h3>Exposures</h3> Among patients treated with chemotherapy during 2007 to 2010 by an oncologist who had not treated patients with bevacizumab in 2005 to 2006, models assessed the association of bevacizumab use with rates of bevacizumab use in their physician's community of connected physicians in 2005 to 2006. Models adjusted for patient and physician characteristics and physician, practice, and community random effects. <h3>Main Outcomes and Measures</h3> Receipt of bevacizumab. <h3>Results</h3> A total of 34 750 patients (14 126 [40.6%] aged ≥75 years; 21 321 [61.4%] female) with cancers of the colorectum, lung, breast, kidney, brain, and ovary were treated with chemotherapy in 2005 to 2006 in the 51 hospital referral regions. Among 9262 patients treated in 2007 to 2010 by 829 physicians whose patients did not use bevacizumab in 2005 to 2006, 3654 (39.5%) were aged 75 years or older and 6227 (67.2%) were female. The rate of bevacizumab use relative to other chemotherapy in 2007 to 2010 by tertile of use (bevacizumab for &lt;4.4%, 4.4%-6.2%, and &gt;6.2% of all patients receiving chemotherapy) among their physician's peers in 2005 to 2006 was 10.0%, 9.5%, and 13.6%, respectively. After adjustment, use of bevacizumab in 2007 to 2010 was greater among physicians in communities with the highest rates of bevacizumab use in 2005 to 2006 compared with those whose peers were in the lowest tertile of bevacizumab use in 2005 to 2006 (adjusted odds ratio, 1.64; 95% CI, 1.20-2.25). <h3>Conclusions and Relevance</h3> This study found that an increase in oncologists' adoption and use of bevacizumab in the years after its approval was associated with their peer physicians being earlier adopters. As organizations seek to provide better care at lower costs, interventions that leverage physician ties may help to promote adoption of high-value use of new cancer treatments and deimplementation of low-value therapies.
Glucocerebrosidase Activity Modulates Neuronal Susceptibility to Pathological α-Synuclein Insult
Authors: Michael X. Henderson, Samantha Sedor, Ian McGeary, Eli J. Cornblath, Chao Peng, Dawn M. Riddle, Howard L. Li, Bin Zhang, Hannah J. Brown, Modupe F. Olufemi, Danielle S. Bassett, John Q. Trojanowski, Virginia M.Y. Lee
Journal: Neuron (2019)
Increased Drp1 Acetylation by Lipid Overload Induces Cardiomyocyte Death and Heart Dysfunction
Authors: Qingxun Hu, Huiliang Zhang, Nicolás Gutiérrez Cortés, Dan Wu, Pei Wang, Jing Zhang, Julie A. Mattison, Eric Smith, Lisa F. Bettcher, Mingyi Wang, Edward G. Lakatta, Shey-Shing Sheu, Wang Wang
Journal: Circulation Research (2020)

Lipid overload-induced heart dysfunction is characterized by cardiomyocyte death, myocardial remodeling, and compromised contractility, but the impact of excessive lipid supply on cardiac function remains poorly understood.To investigate the regulation and function of the mitochondrial fission protein Drp1 (dynamin-related protein 1) in lipid overload-induced cardiomyocyte death and heart dysfunction.Mice fed a high-fat diet (HFD) developed signs of obesity and type II diabetes mellitus, including hyperlipidemia, hyperglycemia, hyperinsulinemia, and hypertension. HFD for 18 weeks also induced heart hypertrophy, fibrosis, myocardial insulin resistance, and cardiomyocyte death. HFD stimulated mitochondrial fission in mouse hearts. Furthermore, HFD increased the protein level, phosphorylation (at the activating serine 616 sites), oligomerization, mitochondrial translocation, and GTPase activity of Drp1 in mouse hearts, indicating that Drp1 was activated. Monkeys fed a diet high in fat and cholesterol for 2.5 years also exhibited myocardial damage and Drp1 activation in the heart. Interestingly, HFD decreased nicotinamide adenine dinucleotide (oxidized) levels and increased Drp1 acetylation in the heart. In adult cardiomyocytes, palmitate increased Drp1 acetylation, phosphorylation, and protein levels, and these increases were abolished by restoration of the decreased nicotinamide adenine dinucleotide (oxidized) level. Proteomics analysis and in vitro screening revealed that Drp1 acetylation at lysine 642 (K642) was increased by HFD in mouse hearts and by palmitate incubation in cardiomyocytes. The nonacetylated Drp1 mutation (K642R) attenuated palmitate-induced Drp1 activation, its interaction with voltage-dependent anion channel 1, mitochondrial fission, contractile dysfunction, and cardiomyocyte death.These findings uncover a novel mechanism that contributes to lipid overload-induced heart hypertrophy and dysfunction. Excessive lipid supply created an intracellular environment that facilitated Drp1 acetylation, which, in turn, increased its activity and mitochondrial translocation, resulting in cardiomyocyte dysfunction and death. Thus, Drp1 may be a critical mediator of lipid overload-induced heart dysfunction as well as a potential target for therapy.
The Term <i>Traumatic</i> in Mild Traumatic Brain Injury and the Misrepresentation of Outcomes—Reply
Authors: Lindsay D. Nelson, Harvey S. Levin, Michael A. McCrea
Journal: JAMA Neurology (2019)

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 Neurology 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 Neurology journal
Collateral Findings from Pragmatic Clinical Trials: What Responsibility Do We Have to Enrolled and Future Patients?
Authors: Danielle M. Whicher, Albert W. Wu
Journal: The American Journal of Bioethics (2020)

Pragmatic clinical trials (PCTs), an important component to achieving a learning healthcare system (Califf and Sugarman 2015), are becoming more common as funding has increased (NIH 2013; PCORI 201...
Facial Asymmetry With Deviated Nasal Tip
Authors: Elizabeth Veasey, Sonya Burton, Janine Malone
Journal: JAMA Dermatology (2019)

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
Corpus Cavernosum Abscess Diagnosed on FDG PET/CT
Authors: Sim Vermeulen, Natascha Walgraeve, Frank De Geeter
Journal: Clinical Nuclear Medicine (2019)

Abstract The utility of PET in septicemia for showing its source and possible metastatic infection has been demonstrated. We describe the diagnosis on PET/CT of a spontaneous corpus cavernosum abscess in a 64-year-old man presenting with Streptococcus constellatus septicemia, in whom the clinical diagnosis had been elusive for 10 days.
CBP mediated DOT1L acetylation confers DOT1L stability and promotes cancer metastasis
Authors: Chaohua Liu, Qiaoyan Yang, Qian Zhu, Xiaopeng Lu, Meiting Li, Tianyun Hou, Zhiming Li, Ming Tang, Yinglu Li, Hui Wang, Yang Yang, Haiying Wang, Ying Zhao, He Wen, Xiangyu Liu, Zebin Mao, Wei-Guo Zhu
Journal: Theranostics (2020)

Background and Aim: DOT1L regulates various genes involved in cancer onset and progression by catalyzing H3K79 methylation, but how DOT1L activity itself is regulated is unclear. Here, we aimed to identify specific DOT1L post-translational modifications that might regulate DOT1L activity and thus impact on colorectal cancer (CRC) progression. Methods: We conducted affinity purification and mass spectrometry to explore DOT1L post-translational modifications. We then established transwell migration and invasion assays to specifically investigate the role of DOT1L(K358) acetylation on CRC cellular behavior in vitro and a bioluminescence imaging approach to determine the role of DOT1L(K358) acetylation in CRC metastasis in vivo. We performed chromatin immunoprecipitation to identify DOT1L acetylation-controlled target genes. Finally, we used immunohistochemical staining of human tissue arrays to examine the relevance of DOT1L(K358) acetylation in CRC progression and metastasis and the correlation between DOT1L acetylation and CBP. Results: We found that CBP mediates DOT1L K358 acetylation in human colon cancer cells and positively correlates with CRC stages. Mechanistically, DOT1L acetylation confers DOT1L stability by preventing the binding of RNF8 to DOT1L and subsequent proteasomal degradation, but does not affect its enzyme activity. Once stabilized, DOT1L can catalyze the H3K79 methylation of genes involved in epithelial-mesenchymal transition, including SNAIL and ZEB1. An acetylation mimic DOT1L mutant (Q358) could induce a cancer-like phenotype in vitro, characterized by metastasis and invasion. Finally, DOT1L(K358) acetylation correlated with CRC progression and a poor survival rate as well as with high CBP expression. Conclusions: DOT1L acetylation by CBP drives CRC progression and metastasis. Targeting DOT1L deacetylation signaling is a potential therapeutic strategy for DOT1L-driven cancers.
Association of miR-141 and miR-200c with time to recurrence (TTR) and overall survival (OS) in resected non-small-cell lung cancer (NSCLC) adenocarcinoma (ADC) patients (p).
Authors: Marc Campayo, Alfons Navarro, Rut Tejero, Maria L Cabanas, Laureano Molins, Ramon M Marrades, Jose Ramirez, Mariano Monzo, Nuria Vinolas
Journal: Journal of Clinical Oncology (2013)

7547 Background: Surgical resection remains the standard curative treatment for early-stage NSCLC, but nearly 50% of p experience recurrence, highlighting the need for novel diagnostic and therapeutic strategies. Moreover, treatments in NSCLC are often histology-dependent, underlining the need for histology-related markers. MicroRNAs (miRNAs) are promising molecular markers in cancer, with marked differences in expression according to histology. miR-200 family members have been associated in vitro with the regulation of epithelial-mesenchymal transition. We have examined their impact on outcome in resected NSCLC p. Methods: We analyzed miRNA expression using TaqMan assays in 160 tumor samples from NSCLC p who had undergone surgical resection and correlated our findings with TTR and OS. Results: p characteristics: age, 67 (51-83); 140 male; 96 (60%) stage I, 34 (21.3%) stage II, 30 (18.7%) stage III; 77(48.1%) ADC, 71(44.4%) squamous cell carcinoma (SCC); 16 (9.1%) received adjuvant treatment. With a median follow-up of 28 months (m), 64 p (40%) had relapsed. TTR for the 107 p with high miR-200c was 26.7 m vs 100.2 m for the 52 p with low miR-200c (P=0.032). OS for p with high miR-200c was 71.2 m vs. 125 m for p with low miR-200c (P=0.01). TTR for 112 p with high miR-141 was 26.7 m vs. 100.2 m for 46 p with low miR-141 (P=0.06). OS for p with high miR-141 was 72 m vs. 118 m for p with low miR-141 (P=0.02). Interestingly, neither miR-200c nor miR-141 correlated with TTR or OS in SCC p. In contrast, in ADC p, the prognostic value of both miRNAs increased: miR-200c (TTR, P=0.01; OS, P&lt;0.0001) and miR-141 (TTR, P=0.003; OS, P&lt;0.0001). This prognostic value was maintained in the subgroup of stage I p: miR-200c (TTR, P=0.011; OS, P&lt;0.001) and miR-141 (TTR, P=0.018; OS, P&lt;0.001). In the multivariate analysis, miR-200c and miR-141 emerged as an independent prognostic factor for OS (OR: 3.2, P=0.006; OR:2.5, P=0.02, respectively) together with age&gt;65 (OR: 3.3, P=0.001) and stage I (OR: 0.3, P=0.004). Conclusions: miR-200c and miR-141 expression is associated with TTR and OS in resected ADC but not in SCC NSCLC p.