tbuckley/cabot-search huggingface dataset:
Influence of dietary calcium on extrarenal synthesis of 1,25-dihydroxyvitamin D3 in mouse colon
Authors: Eniko Kallay, Heide S. Cross
Journal: Cancer Research (2005)

5191  Epidemiological data suggest a protective role of calcium and vitamin D against colorectal tumor pathogenesis. 1,25-dihydroxyvitamin D3 (1,25-D3) is a key determinant of calcium homeostasis and has significant influence on cellular growth and differentiation. Nutritional calcium in the intestinal lumen can act as a growth-regulator and may prevent cancer by direct reduction of colonocyte proliferation. This could occur by modulating colonic vitamin D synthesis. Therefore we proposed to investigate a possible interaction between dietary calcium and the colonic 1,25-D3-synthesizing machinery. Synthesis of 1,25-D3 from its precursor 25-hydroxyvitamin D3 is catalyzed by the mitochondrial cytochrome P450 enzyme, 25-hydroxyvitamin D3-1alpha-hydroxylase (CYP27B1), which is present in human colon carcinoma cells too. 25-hydroxyvitamin D3-24-hydroxylase (CYP24) is the enzyme responsible for the first step in 1,25-D3 catabolism. We investigated the concentration-dependent action of dietary calcium on colonic expression of vitamin D receptor (VDR), CYP27B1, CYP24, and on proliferation as shown by PCNA (proliferating cell nuclear antigen) and p21 expression in a mouse model. Mice were fed a modified AIN-76 diet containing 20 % lactose and 0.9%, 0.1% or 0.04% calcium. We measured calcium content of the feces and found a reduction of fecal calcium content by 80% and 95% in animals fed 0.1% or 0.04% calcium respectively. Low fecal calcium concentration had a promitotic effect on crypt cells. PCNA protein was more than twofold increased already with 0.1% dietary calcium. Quantitative evaluation of the cyclin dependent kinase inhibitor p21 showed less sensitivity to lowered fecal calcium: only the diet containing 0.04 % calcium was able to reduce p21 expression. While low dietary calcium did not affect expression of VDR, we observed a moderate but insignificant increase in CYP27B1 mRNA expression. CYP24 mRNA expression in mice fed 0.9% calcium was much higher in ascending colon than in descending colon. Low calcium diets significantly augmented CYP24 mRNA expression in the ascending colon, without affecting it at all in the descending colon. We confirmed our claim that low fecal calcium content is the regulator of colonic CYP24 expression by showing in vitro, in the Caco-2 colon cancer cell line, that 0.0 mM calcium in a medium without any 1,25-D3 indeed increased CYP24 mRNA levels. We conclude that low dietary and thus luminal calcium concentrations increase proliferation of colonocytes. The concomitant increase in CYP24 levels could result in reduced colonic accumulation of 1,25-D3 during hyperproliferation and unhindered tumor progression. Supported by a grant from the American Institute for Cancer Research, and Jubilaeumsfondsprojekt Nr. 9335.
Diagnostic accuracy of Gram staining when predicting staphylococcal hospital-acquired pneumonia and ventilator-associated pneumonia: a systematic review and meta-analysis
Authors: Otavio T. Ranzani, Ana Motos, Chiara Chiurazzi, Adrian Ceccato, Mariano Rinaudo, Gianluigi Li Bassi, Miquel Ferrer, Antoni Torres
Journal: Clinical Microbiology and Infection (2020)
Metformin Should Be Used to Treat Prediabetes in Selected Individuals
Authors: William H. Herman, Robert E. Ratner
Journal: Diabetes Care (2020)

In this issue of Diabetes Care , Dr. Mayer Davidson proposes that prescription of metformin for patients with prediabetes is inappropriate (1). We respectfully disagree. Hyperglycemia is a continuous risk factor for adverse health outcomes. Both the degree and duration of hyperglycemia are associated with the development and progression of diabetic microvascular and macrovascular complications (2), and early aggressive management of hyperglycemia in both type 1 and type 2 diabetes confers lifelong health benefits (3,4). We believe that Dr. Davidson’s approach to watchful waiting, “to follow [high-risk individuals] closely and immediately introduce metformin when their glycemia meets the criteria for diabetes…,” is inadequate. Numerous studies have demonstrated that there is a delay of 3–8 years between the onset and the diagnosis of type 2 diabetes (5), and at the time of diagnosis as many as 8–16% of patients have diabetic retinopathy, 17–22% have microalbuminuria, and 14–48% have peripheral polyneuropathy (6,7). A recent epidemiologic analysis of new-onset diabetes in the U.K. demonstrated a statistically significant increased risk of microvascular complications at diagnosis among individuals identified previously with prediabetes compared with those with previous normal glucose tolerance (adjusted odds ratio of 1.76 for retinopathy and 1.14 for nephropathy) (8). Therefore, there is no reason to withhold metformin, a safe, effective, and cost-saving treatment to delay or prevent the development of type 2 diabetes, from individuals at high risk. That said, a number of caveats apply.

First, the Diabetes Prevention Program (DPP) and indeed most of the other major diabetes prevention trials studied individuals at extremely …
Consensus of the Italian Primary Immunodeficiency Network on transition management from pediatric to adult care in patients affected with childhood-onset inborn errors of immunity
Authors: Emilia Cirillo, Giuliana Giardino, Silvia Ricci, Viviana Moschese, Vassilios Lougaris, Francesca Conti, Chiara Azzari, Federica Barzaghi, Clementina Canessa, Baldassarre Martire, Raffaele Badolato, Laura Dotta, Annarosa Soresina, Caterina Cancrini, Andrea Finocchi, Davide Montin, Roberta Romano, Donato Amodio, Francesca Ferrua, Alberto Tommasini, Lucia Augusta Baselli, Rosa Maria Dellepiane, Agata Polizzi, Luciana Chessa, Antonio Marzollo, Maria Pia Cicalese, Maria Caterina Putti, Andrea Pession, Alessandro Aiuti, Franco Locatelli, Alessandro Plebani, Claudio Pignata
Journal: Journal of Allergy and Clinical Immunology (2020)
COVID-19 Among American Indian and Alaska Native Persons — 23 States, January 31–July 3, 2020
Authors: Sarah M. Hatcher, Christine Agnew-Brune, Mark Anderson, Laura D. Zambrano, Charles E. Rose, Melissa A. Jim, Amy Baugher, Grace S. Liu, Sadhna V. Patel, Mary E. Evans, Talia Pindyck, Christine L. Dubray, Jeanette J. Rainey, Jessica Chen, Claire Sadowski, Kathryn Winglee, Ana Penman-Aguilar, Amruta Dixit, Eudora Claw, Carolyn Parshall, Ellen Provost, Aurimar Ayala, German Gonzalez, Jamie Ritchey, Jonathan Davis, Victoria Warren-Mears, Sujata Joshi, Thomas Weiser, Abigail Echo-Hawk, Adrian Dominguez, Amy Poel, Christy Duke, Imani Ransby, Andria Apostolou, Jeffrey McCollum
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Although non-Hispanic American Indian and Alaska Native (AI/AN) persons account for 0.7% of the U.S. population,* a recent analysis reported that 1.3% of coronavirus disease 2019 (COVID-19) cases reported to CDC with known race and ethnicity were among AI/AN persons (1). To assess the impact of COVID-19 among the AI/AN population, reports of laboratory-confirmed COVID-19 cases during January 22
Targeting of ubiquitinated proteins to the proteasome: Mechanism and susceptibility to small molecule inhibition
Authors: Raymond J. Deshaies, Rati Verma, Thibault Mayor, Johannes Graumann, Randall W. King, David Fushman
Journal: Cancer Research (2005)

SY16-2  Approval of Velcade by the U.S. Food and Drug Administration for the treatment of relapsed multiple myeloma has validated the ubiquitin-proteasome system (UPS) as a therapeutic target in cancer. The UPS is the principal means by which cellular proteins are degraded. Target proteins are first conjugated with a chain of ubiquitins, and the ubiquitinated protein is then targeted to the proteasome for degradation. Velcade prevents the turnover of ubiquitin-conjugated proteins by binding to the protease active sites in the interior chamber of the 20S proteasome. The proteasome is an extremely complex machine comprising ∼30 different polypeptides. These polypeptides carry out multiple activities that are a prerequisite to the actual proteolytic event that is blocked by Velcade. The activities include: binding of ubiquitinated substrate to the proteasome; opening of a pore so that substrate can gain access to the interior of the 20S proteasome; unfolding of the substrate and its translocation into the 20S proteasome; and cleavage of multiubiquitin chains from the substrate. Given that blockade of 20S protease activity by Velcade has efficacy in combating multiple myeloma, in theory it may be possible to develop new cancer drugs by blocking the other activities of the proteasome. Most recently, we have studied in detail the mechanism by which ubiquitin-conjugated proteins are targeted to the proteasome. Our results reveal that there is a family of different receptor proteins that can functionally engage a ubiquitinated substrate with the proteasome, after which the substrate is degraded. Interestingly, although there is some redundancy among the receptors, there is remarkable specificity as well. This conclusion arises from our observation that different substrates exhibit differential requirements for specific receptors as evidenced from the analysis of protein turnover in mutant yeast that lack particular receptors. Accordingly, it may be possible to stabilize particular subsets of proteasome substrates (and thereby obtain greater specificity and possibly lower toxicity than is achievable with Velcade) with a drug that ablates specific receptor pathways. We already know that the targeting step is drugable in principle, because a blind screen of a 110,000 compound library for small molecules that block protein degradation by the UPS yielded two small molecules - ubistatins A and B - that prevent degradation by binding to the ubiquitin chain and thereby blocking its targeting function. To gain insight into the mechanism by which substrates are sorted to particular receptor pathways, and to identify those pathways that might be the most appealing therapeutic targets, we are developing proteomic methods to identify the ubiquitinated polypeptides that are targeted by particular receptors.
Abstract 2301: Indications for systematic prostate biopsy in men with negative multi-parametric magnetic resonance imaging
Authors: Chidi N. Molokwu, Christos Gkikas, Harry Bardgett, Nicola Lee, Faisal Ali, Rohit Chahal, Rajindra Singh
Journal: Cancer Research (2020)

Abstract Introduction: Multiparametric Magnetic Resonance Imaging (mpMRI) is a valuable tool in the prostate cancer diagnostic pathway, and MRI-influenced biopsy has been shown to be superior to systematic biopsy alone for detecting clinically significant prostate cancer (csPCa), defined as the presence of any Gleason ≥ 4. Negative predictive value of mpMRI for csPCa varies widely in published reports, with a median of approximately 88%. Counselling patients with negative mpMRI (PIRADS score &amp;lt;3)to decide whether or not to proceed with systematic biopsy or PSA monitoring could be challenging. Several studies have shown that a PSA density (PSAD) ≥ 0.15 is an indication for systematic biopsy. We analysed the clinical, radiological and pathological features of patients with negative mpMRI but csPca on systematic biopsy to identify other criteria that may inform the need for systematic biopsy when mpMRI is negative. Methods: For 18 months between Nov 2017 and May 2019, all men on our prostate diagnostic pathway with negative mpMRI were offered systematic biopsy. The criteria for pre-biopsy mpMRI was any man suitable for radical surgery or radiotherapy, plus one or more of PSA ≥ 3, palpable lesion on digital rectal examination, or family history of PCa in a first degree relative (father or brother). mpMRI was performed with a 1.5-Tesla magnet and included T2, DWI and DCE sequences. Systematic biopsy was TRUS-guided, with 8-16 biopsy cores. Results: Of 589 mpMRI scans in 573 men, 216 (37%) had negative mpMRI. Of these, 141 (65%) proceeded with systematic biopsy. Among the men that had biopsy, Gleason 3+3 was detected in 12 men (9%) and Gleason ≥ 4 in six (4%). Important pre-biopsy features in men with Gleason ≥ 4 were PSAD ≥ 0.15 (n=3), artefact on MRI from hip joint prosthesis (n=1), and family history (n=2). There were no unusual histological variants seen on the positive biopsy cores. Conclusion: Most men with negative mpMRI can avoid prostate biopsy and be managed with PSA monitoring. Based on our experience, we recommend systematic biopsy in men with negative mpMRI who have PSAD ≥ 1.5, family history or any imaging artifact that may alter image interpretation. Citation Format: Chidi N. Molokwu, Christos Gkikas, Harry Bardgett, Nicola Lee, Faisal Ali, Rohit Chahal, Rajindra Singh. Indications for systematic prostate biopsy in men with negative multi-parametric magnetic resonance imaging [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2301.
Affordable Care Act Medicaid Expansion and Access to Outpatient Surgical Care
Authors: Anna L. Goldman, Michael K. Paasche-Orlow, Frederick Thurston Drake
Journal: JAMA Surgery (2020)

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 Surgery 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 Surgery journal
Phase I trial of convection-enhanced delivery of IL13RA2 and EPHA2 receptor targeted cytotoxins in dogs with spontaneous intracranial gliomas
Authors: John H Rossmeisl, Denise Herpai, Mindy Quigley, Thomas E Cecere, John L Robertson, Ralph B D’Agostino, Jonathan Hinckley, Stephen B Tatter, Peter J Dickinson, Waldemar Debinski
Journal: Neuro-Oncology (2020)

The interleukin-13 receptor alpha 2 (IL13RA2) and ephrin type A receptor 2 (EPHA2) are attractive therapeutic targets, being expressed in ~90% of canine and human gliomas, and absent in normal brain. Clinical trials using an earlier generation IL-13 based cytotoxin showed encouraging clinical effects in human glioma, but met with technical barriers associated with the convection-enhanced delivery (CED) method. In this study, IL-13 mutant and ephrin A1 (EFNA1)-based bacterial cytotoxins targeted to IL13RA2 and EPHA2 receptors, respectively, were administered locoregionally by CED to dogs with intracranial gliomas to evaluate their safety and preliminary efficacy.In this phase I, 3 + 3 dose escalation trial, cytotoxins were infused by CED in 17 dogs with gliomas expressing IL13RA2 or EPHA2 receptors. CED was performed using a shape-fitting therapeutic planning algorithm, reflux-preventing catheters, and real-time intraoperative MRI monitoring. The primary endpoint was to determine the maximum tolerated dose of the cytotoxic cocktail in dogs with gliomas.Consistent intratumoral delivery of the cytotoxic cocktail was achieved, with a median target coverage of 70% (range, 40-94%). Cytotoxins were well tolerated over a dose range of 0.012-1.278 μg/mL delivered to the target volume (median, 0.099 μg/mL), with no dose limiting toxicities observed. Objective tumor responses, up to 94% tumor volume reduction, were observed in 50% (8/16) of dogs, including at least one dog in each dosing cohort >0.05 μg/mL.This study provides preclinical data fundamental to the translation of this multireceptor targeted therapeutic approach to the human clinic.
Distant-Access Robotic Thyroidectomy—Is It Worth the Cost?
Authors: Nancy D. Perrier, Peter Angelos
Journal: JAMA Surgery (2020)

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 Surgery 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 Surgery journal
The effect of the histone deacetylase inhibitor (HDACi) PXD101 on cell growth and expression of viral and host genes in hepatitis B virus (HBV)-carrying hepatocellular carcinoma (HCC) cell lines
Authors: Brigette Ma, Fion Sung, Qian Tao, Jason H. T. Wong, Gulshan Ara, Winnie Yeo, Anthony Chan
Journal: Cancer Research (2007)

696  Hepatitis B virus infection accounts for 80% of hepatocellular carcinoma (HCCs) in China & integration of HBV DNA into hosts DNA & expression of HBV gene products contribute to HCC pathogenesis. Epigenetic gene silencing is a common event in HCC and histone deacetylase inhibitor (HDACi) is known to reactivate expression of some tumor suppressor genes (TSG) in HCC in vitro (J Hepatol 2004;41:436-45). However, the effect of HDACi on HBV gene expression is unknown. This study evaluated the effect of PXD101, a novel hydroximate that potently inhibits the enzymatic activity of HDACs, on expression of HBV genes (HBx, HBc, HBs) & TSG (p21 gene) in HBV-carrying HCC cell lines: PLC/PRF/5 & Hep3B. The effect of PXD101 on cell growth, apoptosis & histone acetylation (H3,H4 histone) were also studied. When cells were exposed to various concentrations of PXD101 for 24 hr, a dose-dependent inhibition of cell growth was detected with MTT assay: PLC/PRF/5: IC50 = 2.78μM+0.06; Hep3B cells: IC50 = 2.49μM+0.53. Using the Annexin V assay, apoptosis was observed in both cell lines after exposure to PXD101 at IC50 concentration for 24hrs. Using Western Blotting, H3 & H4 acetylation were detected within 1 hr of exposure to PXD101 at IC50 concentration in PLC/PRF/5 & Hep3B cells. Using RT-PCR a dose-dependent reduction of HBx & HBs gene expression at mRNA level was observed in Hep3B but not PCL/PRF/5 cells, following exposure to PXD101 at 5 μM and 10 μM, 2-4 fold higher concentration than IC50 . Interestingly, a time-dependent (1-48 hrs) increase in expression of p21 gene was observed in both cell lines following exposure to PXD101 at IC50 concentration. Methylation-specific PCR showed that p21 was unmethylated in both cell lines at baseline, suggesting epigenetic silencing via mechanisms other than promoter methylation. This study showed that PXD101 can inhibit cell growth, induce apoptosis & histone acetylation in PLC/PRF/5 & Hep3B cell lines. Preliminary result of this study suggests that it may also affect expression of both hosts cellular & HBV genes in HBV-carrying HCC cells. Studies on other TSG & HBV protein expression are ongoing. Based on this result, PXD101 is currently being tested in a phase I/II trial in Asian patients with HBV-associated HCC.
Metastasis-Directed Therapy for Oligorecurrent Prostate Cancer—Not All That Glitters Is Gold
Authors: Alberto Briganti, Giorgio Gandaglia, Francesco Montorsi
Journal: JAMA Oncology (2020)

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 Oncology 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 Oncology journal
Abstract 4119: Utility of ECG to Detect Left Ventricular Hypertrophy Defined by Cardiac MRI in Different Ethnic Groups: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Aditya Jain, Harikrishna Tandri, Darshan Dalal, Harjit Chahal, Elsayed Z Soliman, Ronald J Prineas, Aaron R Folsom, Joao A Lima, David A Bluemke
Journal: Circulation (2008)

Background: Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular event risk. We evaluated the ethnicity-specific diagnostic utility of ECG in the detection of LVH measured by MRI as a gold standard. Methods: 12-lead ECG and MRI of 4498 asymptomatic subjects in the MESA study (49% males, mean age 61 ± 10 years) with no prior cardiovascular disease were analyzed. Left ventricular mass (LVM) was determined from MRI. Body-size predicted LV mass (pLVM) was determined from an allometric height-weight index derived from a subpopulation of 822 normal-weight, normotensive, non-diabetic MESA participants with LVH defined as LVM/pLVM &gt; 1.31 (&gt;95 th percentile). Prediction of absolute LV mass by ECG was also assessed for whites and blacks based on previously validated prediction models for these groups. Results: The study population consisted of 39% Whites, 12% Chinese, 27% Blacks and 22% Hispanics. ECG detection rate for LVH as determined by MRI was significantly more in women than men (12.3% vs 3.9% respectively, p&lt; 0.02). For a specificity &gt;= 90%, the highest overall sensitivity for LVH was shown by Perguia score (28.7%) which increased from the first (17.9%) to fourth quartile (45.3%) of LV mass. At a fixed specificity of 90%, the highest sensitivity was shown by Sokolow-Lyon voltage duration product (SLP) (38.2%). Neither Perguia nor SLP differed significantly across the four ethnic groups with respect to sensitivity and area under the ROC curve (p&lt; 0.27, p&lt; 0.52; p&lt; 0.35, p&lt; 0.88 respectively). Presence of LV strain pattern on ECG showed the highest adjusted odds ratio for LVH across all ethnic groups. ECG predicted LVM correlated significantly with MRI-determined LVM for both whites and blacks (r=0.74, p&lt; 0.001 and r=0.70, p&lt; 0.001 respectively) with no significant difference in LVH detection rates (6.1% vs 9.4% respectively, p&lt; 0.35) Conclusion: Based on LVM prediction models, ECG correlates well with MRI. ECG sensitivity to detect LVH is low and it does not differ significantly between whites and blacks. Based on individual criteria like Perguia and SLP, sensitivity and diagnostic performance of ECG did not vary significantly across different ethnic groups.